mef.hrZAGREB UNIVERSITY SCHOOL OF MEDICINE OFFICIAL JOURNAL / www.mef.hr

Volume 24, No 1

ISSN 1332-960X

• How the Institute was Built . . . . . . . . . . . . . . . . . . . . . . . . . . 3

• Organizing Centre of Excellence . . . . . . . . . . . . . . . . . . . . . 8

• Progress Report on Activitiesof the Institute. . . . . . . . . . . . . . . . . 10

• Research Units . . . . . . . . . . . . . . . . . 19

• Institute Publications for the period 1997 - 2004. . . . . . . . . . . . . . . . . . . . . . 43

Fif

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Special Issue

Special Issue

Since its outset in 1917 theSchool of Medicine at the Univer-sity of Zageb has encouragedequal development of the threebasic constituents of medical sci-ence: clinical medicine, essentialfor restoring health, basic medicalsciences, essential for the develop-ment of medicine as a science, andpublic health, essential for thehealth of the community.

Since its founding, both facultymembers and students of theSchool have been and will contin-ue to be dedicated to excellence ineducation, research and service tothe nation.

The Zagreb School of Medicinehas a distinguished tradition in thefield of neurology as well as sever-al internationally recognizedresearch groups with long-stand-ing research experience in the fieldof neuroscience. Therefore in theearly 90's brain research wasselected as one of the research anddevelopmental priorities.

A Word fromthe Dean

MARCH 2005

phone: +385 1 4564567; fax: +385 1 7897896; e-mail: hiim@hiim.hr; www.hiim.hr

In 1990 the Ministry of Scienceof the Republic of Croatia accept-ed the initiative of the ZagrebSchool of Medicine and supportedthe establishment of the BasicSciences Building and the CroatianInstitute for Brain Research(C.I.B.R.).

In this way, Croatia joined theinternational efforts in the Decadeof the Brain, clearly recognizingthe need for research on the neu-robiological basis and mental dis-orders, as well as the need for amore intensive collaboration withinternational institutions.

The University of Zagreb Schoolof Medicine is also a leading insti-tution in medical education inCroatia. For medical education it isimportant that the major goal ofthe C.I.B.R. is to provide a strongscientific background for graduate(MD), doctoral (PhD) and continu-ing education.

The courses at the School arebased on a well-balanced curricu-lum where students acquire specif-ic skills and knowledge necessaryfor health care. Recently a newPhD program in Biomedicine and

Professor Nada »ikeπ, M.D., Ph.D., Dean

NAME: Croatian Institute for Brain Research

ADDRESS: ©alata 12, 10000 Zagreb, Croatia

USEFULL SPACE: 5500 m2

NUMBER OF REASERCHERS HOLDING Ph. D. DEGREE: 50

NUMBER OF LABORATORIES: 25

PROJECTS: 59

Professor Ivica KostoviÊ, M.D. Ph.D.director and founder

of the Institute

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BACKGROUND

How the Institutewas Built

There are only a few people whoknow exactly what went on “behindthe scene” during the eight turbulentand extremely challenging years(1990-1998) of the construction of theCroatian Institute for Brain Research,which occurred in the midst of the warand during the socially and economi-cally unsettled post-war period of thecountry in transition. Now the con-struction of the academic research in-stitute has been completed and it isfully operating and buzzing with dailyactivity of investigators pursuing theircurrent research goals, no one is partic-ularly interested in “Once upon thetime...” stories. Therefore, I want toshare with a wider academic commu-nity some interesting and almost un-known facts and events, in order tosave them from oblivion.

About the Name

When one has a clear idea about thebasic infrastructure, organization andfaculty, one significant problem still re-mains: what would be a proper desig-nation for a new organizational unit?To name the whole new building theBasic Sciences Building was no problemat all, because we followed the lead ofU.S. Schools of Medicine where a sig-nificant portion of basic research is usu-ally concentrated in such units. How-ever, it was not so easy to find a propertitle for the brain research unit. First ofall, the basic idea has always been toestablish an internationally recognizedacademic research unit, and the word“institute” has a somewhat differentmeaning in English than in Croatian. Inaddition, although in the early 1990sthe word “Croatian” was extremely ac-ceptable for both Croatian people andthe members of the academic commu-nity, it was clear from the outset thatten or twenty years later it would prob-ably be one of the very few academicunits with an explicitly national attrib-ute in its name. However, with a littlehelp from wise members of our Inter-national Scientific Advisory Board, I rec-ognized an instructive example in “TheNetherlands Institute for Brain Re-

search” in Amsterdam. The Nether-lands, widely recognized as one of themost liberal states in Europe, foundedits central institute for brain research atthe beginning of the 20th centurywithin the framework of the BrainCommission efforts to establish an in-ternational and inter-academic net-work of central national institutes foradvancing the research on the struc-ture, functions, development and dis-orders of the human brain. Thus, justbefore the outbreak of the First WorldWar, Europe had already launched itspioneering effort to establish what was(almost a century later!) known as “TheDecade of the Brain”. Those instituteswere sponsored by national academiesand were officially proclaimed to becentral national institutes for brain re-search (e.g. Obersteiner’s institute inVienna, von Monakow’s institute inSwitzerland, Vogt’s institute in Berlin,etc.). Therefore, the Dutch Academy ofArts and Sciences founded The Nether-lands Institute for Brain Research, ledby Cornelius Uddo Ariens Kappers.With similar objectives in mind, theCroatian Institute for Brain Researchrepresents our national contribution tothe international network initiative foradvancing neuroscience during “TheDecade of the Brain” and “The Centuryof the Mind”.

About theConstruction

From the outset, the construction ofthe Basic Sciences Building and the Cro-atian Institute for Brain Research wasexposed to periodic (and often mali-cious) criticism, most probably initiatedby some lobbying groups with differentagendas, and spread through the gos-sip and ill-fated commentaries in cer-tain media. One common thread insuch gossip and criticism was focusedon the supposedly “flamboyant roof”and more specifically on the “marblecolumns and pavements” of the Insti-tute. However, nothing could be fur-ther from the truth. There is no marblein the Institute, and it is paved with the

Dear readersand friends,

I am privileged to be theguest-editor of mef.hr and mostgrateful to Professor Marko Pe}i-na, the spiritus movens of thisbulletin and our Medical Schoolin general, who provided mewith the opportunity to shapethis special issue devoted to the15th anniversary of the CroatianInstitute for Brain Research(CIBR).

As you may or may not know,the Croatian Institute for BrainResearch is an integral part of theZagreb Medical School and Za-greb University. Due to the ex-traordinary efforts and for-ward-looking leadership of itsfounder and current director,Professor Ivica Kostovi}, since itsinception 15 years ago, CIBR hasgrown into a respectable, inter-nationally recognized institution.

I sincerely do hope that you willfind the information publishedhere both informative and inter-esting. A lot more is available atthe official web site of the Insti-tute www.hiim.hr. On thesepages you will also find all neces-sary information related to theactivities of the Brain AwarenessWeek. I cordially invite you to joinus in celebrating our Anniver-sary!

With best wishes,

Goran [imi}

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same granite which is found in Ilicastreet – the only difference being thatwe used a well-polished version of thatgranite. Moreover, the same type ofplates on Institute’s outer walls, to-gether with highly reflective windowsand blue-and-white glass plates, havebeen used to ensure the most efficientuse of energy (especially for coolingduring hot summers), thus enabling upto 30% lower energy costs per year. Infact, there was a time when, underpressure from the media, ProfessorJuraj Geber (at that time Vice-dean forFinances) and myself almost gave up onthat type of outer walls; however, Pro-fessor Jeren (at that time the Ministerof Science & Technology) strongly in-sisted that we should proceed with theoriginal construction plan, because asan engineer he clearly recognized thelong-term cost-benefit advantages ofthat design. I remember well that, stillsomewhat worried about the shiny pol-ish of the granite plates on the outerwalls, I suggested that we may spraythem with acid or something, in order

to make them rough and less shiny. Thearchitect, Zlatko Juri}, was utterlyshocked by such a proposal, and beganfrantically lobbying against the realiza-tion of such a crazy idea. I had to con-fess that it was, in a way, my little re-venge for his somewhat exuberant de-sign of the building – but I finally gaveup the idea of using the acid. Speakingabout outer walls, it should be pointedout that the cornice consists of blueplates, which were purchased fromGermany at practically the same priceas the ordinary ones.

I would like to mention a few detailsrelated to the war and its dangers atthat time. A new law has been passed,and it was no longer required to have afallout shelter in a newly constructedbuilding. However, there was a war,and shells were hitting Zagreb itself, aseveryone still well remembers. With re-spect to that, I followed a bit of goodadvice of the late general Janko Bo-betko, who convinced me that there isreally no need to construct such a shel-ter – especially when one realizes that

the sheer quantity of concrete used inthe construction of the building alreadymakes it shell-proof. Thus, we saved al-most 600.000 Euro during the con-struction!

Many aspects of the constructionwere in fact strictly regulated and re-quired by new Croatian laws (which inthis respect followed the lead ofcurrent European laws). The newly con-structed research building had to meetrigorous standards for biosafety andlaboratory safety, significantly impro-ved and environment-friendly sewageand waste-care systems, as well asspecially controlled conditions for labo-ratory animal care and use facilities. Asour laws are still being rewritten inaccordance with European standards,it happens that different laws and re-gulations are sometimes not well-co-ordinated or even contradict one ano-ther. Thus, it took us much longer toobtain a chimneysweeps permission touse the chimney than to complete theconstruction of the entire building!Similarly, the elevator doors were builtaccording to strict and expensive Swe-dish standards – but we were simplyunable to obtain local permission fortheir use and finally had to rebuild theelevators!

There is another thing I have toconfess: I find the wall-drilling and lea-king of the roofs extremely disturbingand irritating, because I spent longyears working in the basement of theDepartment of Anatomy “Drago Pero-vi}”, almost constantly exposed toill-conceived and totally unprofessio-nally conducted drillings and constru-ction failures of all kinds. Thus, I had asingle request for the constructors ofour new building: “I beg you, do any-thing but save me from any wall drillingand chiselling - and do not let the roofleak at the first heavy rain!” And guesswhat happened when the Institute wasfinally opened? The first thing to dowas wall-drilling and chiselling in orderto fit in a new kind of elevator doors!Do I have to say that the roof started toleak during the same month, despiteuniversal claims that copper roofs arefoolproof and expertly constructed? Iwas furious, but the engineers andpeople responsible for supervising theconstruction calmly and flatlyresponded as follows: “You know, wedid an excellent job. So, it must be thepigeons or other birds, who pecked thesilicon fillings between the roofplates!”

Sequence of documents relevant for the establishment of the Institute, from theleft: letter of support of the first Croatian president, Dr. Franjo Tu|man, givingimpetus to the whole idea; decision of the Academic Senat of the Zagreb MedicalSchool, and Certificate of incorporation of the Zagreb Commercial Court.

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About theSelf-fulfillingProphecies whichNevertheless EndedHappily

For several years I had been wonder-ing, why people were not very excitedabout the whole project and did not of-fer a strong and constant opposition toit (as it is unfortunately so common inCroatia). Then I slowly realized thatthey in fact simply did not believe thatthe project would ever be finished!Many of them reasoned like this: “Justwait and smile – there will be a big fussand finally nothing will come out f it.Kosta (that is my nickname) is buildingthe mausoleum for himself, but will faillike others. And, you see, he is now apolitician, overburdened with adminis-trative and humanitarian duties, he willsoon drop out of research, he will losehis international contacts, he will loseassistants and students, and he will endup empty-handed”. Each sequence ofcriticisms was quite predictable and re-shaped at every new successive step to-wards the completion of the building.First they said “It will never get off theground”. Then they said “Oh, it will al-ways remain just crude walls – Rohbau,you know”. Then it was described as“an unfinished Disneyland which willnever really open”. When it was finallyconstructed and opened, they said “Itwill always remain empty, the old guyswill retire and there will be no young in-vestigators to work in it!”. Perhaps theglaring example of such a lack of faithwas an article published in “Nature”(volume 365, September 30, 1993) un-der the title “Brain institute falls victimto war in ex-Yugoslavia”. However, onanother occasion Professor Lackovi}presented the project of the Institute asthe single scientific program which

Croatia was able to present to the Euro-pean COST initiative during the war. Hisaudience was simply stunned – theyjust could not believe that in the midstof the cruel and terrible war, Croats hadfound the strength and courage to pro-ceed with the modern research pro-gram in neuroscience!

I am really proud and glad to saythat, after ten long years of arduousefforts, strenuous fighting against allkinds of obstacles, and despite the li-mited funding resources, the CroatianInstitute for Brain Research and BasicSciences Building are alive and well.Our students finally enjoy decent andversatile facilities for teaching andresearch, our young investigators be-gin to thrive in modern and well-equipped laboratories which theyincreasingly appreciate (especiallyafter they have spent a few years inlaboratories and institutes abroad!),our projects are ongoing and the

stream of publications in internationaljournals flows steadily and willprobably increase in the near future.

One final curiosity – as the founderand main initiator of the wholeproject, I did not manage to attend theopening ceremony when the Institutewas finally completed! I was preven-ted by certain state duties and ob-ligations – but although politics andthe war often prevented me to enjoythe daily work at the Institute duringits construction and in the years im-mediately following its opening, theydid not prevent the completion of thewhole project and did not stop mefrom returning to full-time researchand teaching as I am approaching themature years of my travel along theroads of the Brainland.

Ivica Kostovi}

Front view of the Basic Sciences Building - main entrance

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About the Croatian Institutefor Brain Research

The Croatian Institute for Brain Re-search (CIBR) is a teaching and researchinstitute of University of Zagreb Schoolof Medicine in which multidisciplinaryteams of basic and clinician scientistsstudy the nervous system and thecauses of neurological diseases and de-velopmental brain disorders.

A Pioneering Mission

The CIBR was established in 1990 inresponse to the need for an integratedapproach to solve important issues inneuroscience research. The purpose informing the CIBR was to bring togetherin neighboring laboratories a group ofinvestigators experienced in the majordisciplines of basic and clinical neuro-science, with the goal of furthering theunderstanding of neurobiology of hu-man cognitive development and its dis-orders at the cellular and molecularlevel. From the spring 1999, the CIBR islocated in the newly constructed BasicScience Building at the School of Medi-cine campus.

A Combination of Basicand Clinical Neuroscience

At present, the CIBR is a stimulatingacademic environment in which re-search and teaching come together toadvance knowledge of the nervous sys-tem and improve the diagnosis andtreatment of patients with nervous sys-tem diseases and disorders. The conge-nial research setting actively fosters col-laboration between investigators whohave different areas of expertise. Over50 faculty members contribute their re-search and clinical strengths to mul-tidisciplinary teams. The faculty of theCIBR have appointments in the depart-ments of Neuroscience, Anatomy, His-tology & Embryology, Pathology, Physi-ology, Pharmacology, Biology, Chemis-try & Biochemistry, Neurology, Neuro-surgery, Psychiatry and Radiology. Inaddition, the extramural collaboratorsof the CIBR have appointments in theuniversity departments of Physics &Biophysics, Psychology, Linguistics &Phonetics, and Education & Rehabilita-tion and with the Institute “RudjerBoskovic”. Clinical research activity iscarried out in coordination with theClinical Hospital Center Zagreb (thelargest university hospital in Croatia),

as well as other university-affiliatedhospitals and with the Institute “RudjerBoskovic”. Together with students andfellows, CIBR investigators pursue mul-tiple areas of inquiry including normaldevelopment of the human cerebralcortex, developmental brain disorders,signaling mechanisms and molecules inthe developing and adult brain, the CSFpathophysiology and hydrocephalus,neurodegenerative diseases, andschizophrenia.

A major strength of the CIBR is thecapacity to study the brain using thecombined perspectives of clinical andbasic research. The main area in whichbasic and clinical science are inter-twined in daily practice at the CIBR isbrain plasticity and repair afterperinatal hypoxic/ischaemic lesions inpremature infants. Among the CIBR'sinternationally recognized strengthsare research on development of the hu-man cerebral cortex and the extensiveand versatile Zagreb Neuroembryo-logical Collection.

Teaching and InfrastructureResources

The CIBR and the School of Medicineoffer a comprehensive training pro-

grams for graduate students, PhD stu-dents, postdoctoral fellows, and resi-dents in neurology, neurosurgery andpsychiatry. Well structured neurosci-ence program exists within theBiomedicine and Health PhD programat the School of Medicine in Zagreb. Re-cently, also, a multidisciplinary pro-gram in neuroscience was initialised atthe level of the University ii Zagreb. TheCIBR harnesses state-of-the-art techni-cal resources for scientific advance-ment, including the electron micros-copy, confocal microscopy, 2Tesla MRIunit, and modern information technol-ogy infrastructure. Trainees are a vitalpart of the CIBR. Whatever their spe-cialty, students receive a breadth of ex-posure to basic and clinical neurosci-ence. The CIBR's research includes mo-lecular, cellular, and systems neurobio-logy; neuroimaging; improved neuro-surgical methods; neuropsychology;neurolinguistics; and all aspects of dis-ease-oriented programs. The MSc andDSc programs are flexible. While labo-ratory research predominates, surveyas well as highly specialized postgradu-ate level and continuing educationcourses are available within the CIBRand other School of Medicine centres.Students are encouraged to attend re-

Members of Neuroanatomical section of the Zagreb University Medical SchoolInstitute of Anatomy. Picture was taken in 1987.

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search seminars and journal clubs andhave many opportunities to presenttheir own work.

International Schools

The first FENS/IBRO Summer Schoolwas held in Dubrovnik and Zagreb in2003, and mobilized member of theCIBR, brought foreign speakers toCroatia and attracted students from 17countries.

The second FENS/IBRO SummerSchool will be held in Zadar and Zagrebfrom September 24th to October 4th,2005.

A Manageable Size

The relatively small size of the CIBRand its highly concentrated clinical andresearch resources are underlyingstrengths that promote the vital peopleconnections often absent in larger in-stitutions. Interpersonal relations at theCIBR are informal and non-hierarchical.At the same time, the environment islarge enough to be stimulating, withsufficient scope to put initiative andideas into practice.

Interaction with Public: Increasingthe Visibility of Brain Research

An important goal of the CIBR is toinform the general public and decisionmakers about the importance of brainresearch. Therefore, the CIBR is the seatof the Croatian Society for Neurosci-ence (CSFN) and of the IBRO liaison of-fice in Croatia. The CSFN is member ofthe Federation of European Neurosci-ence Societies (FENS) and the Interna-tional Brain Research Organization(IBRO). The CSFN aims to advanceknowledge about the personal andpublic benefits of neuroscience and todisseminate information on the brain,in health and disease, in an accessibleand relevant way. The CIBR and theCSFN are both deeply involved in the in-ternational commitment to increasingawareness of the brain and the impor-tance of brain research, through orga-nizing Brain Awareness Week in Croatiaand taking part in other activities of TheEuropean Dana Alliance for the Brain(EDAB), the FENS, and the IBRO. TheCIBR and the CSFN are also intenselyengaged in establishing fruitful and ef-ficient collaboration with diverse pa-tient groups and associations inCroatia.

An Institution in Progress

The CIBR is vigorous and growing. Inpursuit of its goals, the CIBR is consoli-

dating strengths, incorporating newmethods and techniques, and recruit-ing researchers who can make impor-tant contributions to their fields.

Planning for the Future: ProvidingStrong Leadership and ScientificDirections

The CIBR has set an ambitious goal:to be at the leading edge of develop-ments in neuroscience, and to emergeas Croatia's centre of excellence for re-search in basic and clinical neurosci-ence. Our many advantages make this arealistic aim. Ongoing research activi-ties provide us national and interna-tional visibility. We are developing newapproaches and incorporating newtechnology and methods that will pavethe way for significant advances. And

we benefit from our affiliation with theoldest and largest University andSchool of Medicine in Croatia.

Two main mechanisms exist to en-sure our continuing vitality, both scien-tific and institutional: (1) The Interna-tional Scientific Advisory Board, com-prised of basic and clinicalneuroscientists from leading medicalcentres around the world, who evalu-ate programs in the CIBR periodicallyand measures their effectiveness usingthe highest international standards. (2)The internal Research Advisory Board,made up of research group leaders andcoordinators, meets monthly with theCIBR's Director to debate future re-search directions, discuss interactionswith the School of Medicine and itsclinics, and review recommendationsfor hiring and education of young in-vestigators.

Research organization of the CIBR

Organizational structure of the CIBR

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Organizing Centre of Excellenceand Long-term Program Projectin Human Neurobiology

Neuroscience is the most rapidlygrowing field of science. Recently, asignificant advance has been made inthe area of disclosing molecular basisof neurological and psychiatric disor-ders. For a small country with limitedbudget resources it is difficult to stimu-late and finance large-scale productiveand novel research in this importantarea of basic and clinical sciences. In or-der to concentrate national scientificefforts, establish the basis for fruitfulinternational cooperation, and contrib-ute to the European Decade of theBrain, the Croatian Institute for BrainResearch was founded in early 1990s atthe School of Medicine, University ofZagreb. The following criteria were de-fined in this joint university-Ministry ofscience project: a) cooperation be-tween basic and clinical neuroscienceresearchers b) supervision by interna-tional Scientific Advisory Board, c) uni-versity affiliation with joint appoint-ments of Faculty staff in education andteaching, d) development of thelong-term research project centredaround several themes related to majorcognitive disorders, e) the infrastruc-ture and resources to be centredaround research core centres and mul-tiple project centres. In order to assurethe transfer of knowledge, Centre forClinical Application of Neuroscienceand Diagnostic Centre «Neuron» werefounded and situated in the samebuilding as the Institute, all three usingthe common infrastructure and sharingthe staff. Long-term research programproject entitled «Neurobiology of Cog-nitive development and cognitive disor-

ders» was subdivided in three majorthemes.

Theme A: Reorganization, Plasticity,Damage, Repair, and Recovery of theHuman Brain After Structurally DefinedPerinatal Lesions; Theme B: Neuro-biology of Neurological and MentalDisorders with Cognitive Disturbances;Theme C: Molecular Pharmacology ofBehaviour and Biochemistry of Neuro-transmitters and Second Messengers.

Since 1998, the most intensive coop-eration was initiated within the frame-work of theme A, when researchgroups moved into new facilities of therecently built Basic Science Building.This long-term project developed in areal centre-core project with interdisci-plinary approach spanning all areas ofhuman development from basic neu-roanatomy to neurolinguistic develop-ment and including researchers fromthe entire University and major Univer-sity Clinics in Zagreb and the Institute«Ruder Boskovic». These efforts lead (in2003) to expanded program entitled:«DEVELOPMENT, PLASTICITY AND RE-PAIR OF THE BRAIN AFTER PERINATALLESIONS» dealing with,

1. ETHIOLOGY and PATHOPHYSIO-LOGY (preterm birth, antenatalevents, fetal hypoxia);

2. STRUCTURAL and CHEMICAL RE-ORGANIZATION (axonal path-ways, guidance molecules, syn-apse formation, dendritic devel-opment, cell death, normal andgenetically disturbed develop-ment);

3. NEURODEVELOPMENTAL and CO-GNITIVE OUTCOME (neurological

and cognitive development, struc-tural 3D-MRI images) and,

4. MOLECULAR MECHANISMS (genefunction in mouse CNS, molecularbasis of plasticity, second messen-gers, wnt signalling, serotonergictransmission).

The long-term international coopera-tion is established with Department ofNeuroscience Yale University School ofMedicine, The Netherlands Institute forBrain Research, Karolinska Institutet,INMED-INSERM and several other cen-tres. It is crucial that projects cooperat-ing in the field of normal and disturbeddevelopment (theme A) are focused onmajor developmental neurological andcognitive disorders. Thus, they contrib-ute to national health care system anddevelopment of basic-clinical coopera-tion.

The special projects of the CroatianInstitute for Brain Research (ZagrebNeuroembryological Collection & BrainBank) are tightly related to the mainlong-term objectives of the pro-gram-project and are planned to be in-corporated in the European Neuroem-bryological Network and EuropeanBrain Bank Network, as well as similarnetworks in the USA. Long-term re-search goals, established basic-clinicalcooperation, several research core cen-tres and multiple project centres, Uni-versity affiliation, and established inter-national cooperation all qualify theCroatian Institute for Brain Research aspotential Centre of Excellence in Neuro-science, not just for Croatia but also forbroader region in this part of Europe.

Ivica Kostovi}

Over the next several years, the CIBRwill make a major commitment to threeresearch disciplines: molecular neu-robiology, cellular neurophysiology,and cognitive neuroscience. These re-search disciplines, which were previ-ously practically nonexistent in Croatia,provide new ways of approaching bio-medical research and hold enormouspotential for enriching our understand-ing of the nervous system and for de-

veloping improved methods of clinicaldiagnosis and treatment. The Institutewill also strengthen neuroimaging anddevelopmental neuropathology, bothto meet the clinical needs of our collab-orative hospitals and to enhance thecollaboration with other CIBR groups.

We recognize that in a competitivescientific world, the CIBR's strength willbe measured only by the impact of thecontributions we make tomorrow. Our

responsibility is to advance the neuro-science research in Croatia. This we willaccomplish by continually imposinghigh standards of excellence and integ-rity on our work, and by creating astimulating environment in which clini-cal care and research thrive together.

Ivica Kostovic

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Neuroscience in CroatiaThe major impetus for neuroscience

in Croatia occurred in early 1990s, con-comitantly with the onset of The De-cade of the Brain, when a group of en-thusiasts at the School of Medicine Uni-versity of Zagreb initiated the project ofthe Croatian Institute for Brain Re-search (CIBR). From the beginning, theprogress of the project was evaluatedby the International Scientific AdvisoryBoard.

Croatian Government responded fa-vorably to the initiative: initial fundswere raised for the construction of Ba-sic Science Building - CIBR at the Schoolof Medicine Zagreb. However, despitethe initial success, the continuation ofthe project became arduous. Namely,as a consequence of the war in Croatiaplus socioeconomic problems charac-teristic for all «transitional» countries,the environment in Croatia was not veryfavorable for new projects and long-termresearch goals.

However, by the end of 1998, severalleaps forward were acomplished: theCroatian Parliament passed a new Na-tional Research Program which for thefirst time recognized brain research,and long-term program «Neurobiologyof cognitive development and cogni-tive disorders» was approved; the con-struction of the Basic Science Buildingwas completed and the CIBR finally be-gan to fullfil its pioneering mission; theCroatian Society for Neuroscience(CSFN) was founded in 2001, became amember of FENS and IBRO in 2002, andhas rapidly grown from 127 membersin 2001 to 223 members in 2004. Thereis also a neuroscience program withinthe Biomedicine & Health PhD programat the School of Medicine Zagreb, andmultidisciplinary program in cognitiveneuroscience at the level of Universityof Zagreb. The first FENS/IBRO SummerSchool was held in Dubrovnik andZagreb in 2003, and mobilized mem-bers of the CSFN, brought foreignspeakers to Croatia and attracted stu-dents from 17 countries. The secondIBRO/FENS Summer School will be heldin Zadar and Zagreb from September24 to October 04, 2005.

The CIBR harnesses state-of-the-arttechnical resources (including electronand confocal microscopy, 2 Tesla MRIunit and modern information technol-ogy). The congenial research setting ac-tively fosters collaboration between in-vestigators who have different areas ofexpertize in basic and clinical neurosci-

ence. Investigators at the CIBR and affil-iated centers pursue multiple areas ofinquiry including developmental neu-robiology and neuropathology, signal-ing mechanisms, the CSF pathophy-siology, neurodegenerative diseases,stroke and schizophrenia. There is onecollaborative long-term research pro-ject entitled «Development, plasticity,and Repair of Brain after Perinatal Le-sions». Other basic and clinical neuro-science research groups have other in-dividual projects in Zagreb, Split, Osijekand Rijeka. As a single clinical site out-side the EU countries, CIBR's Section ofPsychopharmacology became in 2004the full member of European Commis-sion funded (FP6) scientific project«Genomic-based therapies for depres-sion».

The CSFN is deeply involved in the in-ternational commitment of increasingawareness of brain research, throughorganizing Brain Awareness Week inCroatia and taking part in other activi-ties of The European Dana Alliance forthe Brain (EDAB).

Despite the growing number ofmembers, the intensive presence in sci-entific community and productive re-search of its members, the CSFN is stillfighting for the full recognition of neu-

roscience in Croatia as a new field ofscientific research. During its annual as-sembly in December 2004, the CSFN is-sued a Declaration on Neuroscience,asking scientific and administrative au-thorities in Croatia to accept neurosci-ence as a research field equal to othermajor fields of scientific research, as in-dicated by recent developments in theneuroscience and position of neurosci-ence in leading journals such as Natureand Science, and leading academic in-stitutions.

In the future, members of CSFN willcontinue to have focused research cen-tered around major disorders of brainand develop more teaching programsin neuroscience at Croatian universi-ties. International cooperation is ex-pected through international schools,IBRO/FENS schools, joint research pro-jects within the future European FP7program, better evaluation of scientificprograms through international advi-sory board and IBRO services.

Milo{ Juda{

Practical lession - professor Milo{ Juda{ (right) with his students

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PROGRESS REPORT

Activities of the Croatian Institutefor Brain Research, Schoolof Medicine, University of Zagreb(May 31, 2000 TO April 27, 2004)

Progress report on Institute's program and activities, by Director, Prof. dr. sc. Ivica Kostovi}, according to Articles 61 & 62 ofthe Statutes of the Croatian Institute for Brain Research.

ORGANIZATIONAL UNITSDEVELOPED DURING THE MANDATEPERIOD (CURRENT STATUS)

The Croatian Institute for Brain Research (CIBR) is one ofmajor research and teaching units of the School of Medicine,University of Zagreb, recognized by the Statute of the Schoolof Medicine as well as legally registered. The current directorof the CIBR is Professor Ivica Kostovi}, MD, DSc. At present,the CIBR has the following active organizational units:

Department of Neuroscience(head: Professor Hrvoje Banfi}, MD, DSc)

Section of Developmental Neuroscience(head: Milo{ Juda{, MD, DSc, Associate Professor)Laboratory for Neurohistology and Chemical Neuro-anatomy (Head: Milo{ Juda{, MD, DSc, Associate Pro-fessor)Laboratory for Developmental Neuropathology (Head:Goran [imi}, MD, DSc; Assistant Professor)Laboratory for Neuromorphometry (Head: Zdravko Pe-tanjek, MD, DSc)

Section of Neurogenetics, Cytogenetics & DevelopmentalGenetics (head: Sre}ko Gajovi}, MD, DSc, Assistant Pro-fessor)Laboratory for Neurogenetics & Developmental Genet-ics (head: Sre}ko Gajovi}, MD, DSc, Assistant Professor)Laboratory for FISH (head: Lukrecija Bre~evi}, PhD, As-sistant Professor)Laboratory for Medical Genetics (head: Professor NinaCanki-Klain, MD, DSc)

Section of Electron Microscopy (head: Professor LjiljanaKostovi}-Kne`evi}, MD, DSc)

Section of Biochemistry & Molecular Biology (head: Profes-sor Hrvoje Banfi}, MD, DSc)Laboratory for Second Messengers (head: ProfessorHrvoje Banfi}, MD, DSc)Laboratory for Radioactive Nuclides (head: VladijanaCrljen-Manestar, MD, DSc)Laboratory for Cell & Tissue Cultures (head: Dora Vi{nji},MD, DSc, Assistant Professor)Laboratory for Molecular Neurobiology & Neuroche-mistry (head: Marija Heffer-Lauc, MD, DSc, AssistantProfessor)

Section of Neurophysiology (head: Marijan Klarica, MD,DSc, Associate Professor, & Professor Emeritus MarinBulat, MD, DSc)Laboratory for Neurophysiology(not yet fully established - research coordinator: MilanRado{, MD, MSc)Laboratory for Neuropathophysiology of the CSF (head:Marijan Klarica, MD, DSc, Associate Professor)Laboratory for Experimental Neurosurgery (head: PavleMikli}, MD, DSc, Associate Professor)

Other Organizational Unitsof the CIBR

Section of Neuroimaging & MRI Unit (deputy head: MarkoRado{, MD, DSc)

Section of Neuropsychopharmacology & Behavioral Pharma-cology (head: Neven Henigsberg, MD, DSc, Assistant Professor)

Section of Clinical Research in Neuroscience (head: Profes-sor Juraj Geber, VMD, DSc)

Zagreb Neuroembryological Collection and Brain & TissueBank (head: Bo`o Kru{lin, MD, DSc, Associate Professor)

Section of Laboratory Animals Care & Use (head: ProfessorHrvoje Banfi}, MD, Dsc)

Associated laboratories in Basic Science Building (repre-sentative: Prof. dr. sc. Melita [alkovi}-Petri{i}, MD, DSc, As-sistant Professor)

The following collaborating institutions have official longterm collaborative contracts with the CIBR: Diagnostic Center

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«Neuron» with units for Neuroradiology, Pathology, Cyto-genetics and Psychiatry; Clinical Center for Research in Neu-roscience; Center for Mental Health (joint venture of ClinicalHospital Zagreb and School of Medicine); Center for Re-search on PerinatalOrigin of Neurological and Cognitive Dis-orders.

The above mentioned institutions have the following labo-ratories at the CIBR: Laboratory for Behavioral Neurophar-macology (head: Professor Vera Folnegovi}-[malc, MD, DSc);Laboratory for Developmental Neurolinguistics (head: Pro-fessor Marta Ljube{i}, PhD); Laboratory for DevelopmentalNeurology (head: Vlatka Meja{ki-Bo{njak, MD, DSc, Associ-ate Professor); Laboratory for EEG and Evoked Potentials(head: Tomislav Gojmerac, MD, MSc & Goran Ivki}, MD); Lab-oratory for Developmental Cognitive Psychology (head: Mir-na Kostovi}, MSc).

Extramural Laboratories

Laboratory for Molecular Neuropharmacology, InstituteRu|er Bo{kovi} (head: Branimir Jernej, MD, DSc)

Laboratory for Neurochemistry and Molecular Neurobio-logy, Institute Ru|er Bo{kovi} (Head: Darko Ore{kovi}, MD,DSc)

Teaching Coordination

Teaching coordination is conducted through the Depart-ment of Neuroscience, which has a status of Chair in Neuro-science (head: Professor Hrvoje Banfi}, MD, DSc).

International Scientific Advisory Board

Present members of the International Scientific AdvisoryBoard are (in alphabetical order): Yehezkel Ben-Ari, Jack Dia-mond, Mirko Diksic, Philippe Evrard, Pedro A. Ferchmin,Tamas F. Freund, Giorgio M. Innocenti, Oleg A. Krishtal,Kre{imir Krnjevi}, Ante L. Padjen, Roland Pochet, Pasko Rakic,Mirjana Randic, Ronald L. Schnaar, Nenad Sestan, Dick F.Swaab, Harry B.M. Uylings, and Bengt Winblad.

Research Projects

The research is organized through long-term intramuraland extramural research program project in neuroscience en-titled «Neurobiology of Cognitive development and Cogni-tive Disorders», which has been subdivided in three majorthemes encompassing 41 individual projects:

Theme A: Reorganization, Plasticity, Damage, Repair, andRecovery of the Human Brain After StructurallyDefined Perinatal Lesions (coordinator: Profes-sor Ivica Kostovi}).

Theme B: Neurobiology of Neurological and Mental Disor-ders with Cognitive Disturbances (coordinator:Professor Vera Folnegovi}-[malc).

Theme C: Molecular Pharmacology of Behaviour and Bio-chemistry of Neurotransmitters and Second Mes-sengers (coordinator: Professor Hrvoje Banfi}).

It is important to emaphasize that research at the CIBR is fi-nancially supported through individual awards for individualresearch projects. Thus, grant contracts stimulate diversetopics, meaning that research topics at the CIBR cover abroad spectrum, from molecular neurobiology to cognitivesciences.

It also means that every individual investigator has to com-pete for research money with all other research groups at theUniversity and in the Croatia, and to suffer the same (ratherstrict) limitations with respect to the employment of younginvestigators.

Only recently (winter 2003), Ministry of Science & Educa-tion has awarded a small grant (cc 40.000 Euros) for the co-ordination of Theme A (Development). This new collabora-tive project entitled: «Development, Plasticity, and Repair ofBrain After Perinatal Lesions» will fe funded with the sameamount in 2004 and will be core for increasing the coopera-tion between different groups and focus it on cellular topicsof joint interest.

Human research potential, consisting of more than 30doctors of science, are evenly involved in the realization ofintramural projects.

Appointments: All faculty staff has primary appointmentsin teaching at different Chairs of the School of Medicine.

The main body for coordination of scientific programs isInstitute's Faculty Board which according to the Statutesconsists of: heads of Sections and directors of research pro-grams.

School of Medicine, represented by the CIBR, has long-termcontracts for cooperation with Clinical Center «Zagreb» - Hos-pital Rebro and with daughter-institutions Clinical Center forResearch in Neuroscience and Diagnostic Center «Neuron»(which uses MRI apparatus under the contract), and Centerfor Research on Perinatal Origins of Neurological and Cogni-tive Disorders – in order to assure the transfer of knowledge.

SCIENTIFIC PROGRAM AND TOPICS

Projects

As our research topics cover a broad spectrum from molec-ular neurobiology to cognitive sciences, individual projectsare currently grouped in two main divisions:

1. Projects within the collaborative project (see enclosed)2. Other intramural projects (see enclosed)

International Cooperation

All laboratories have an established international scientificcollaboration with exchange of scientists and joint publica-tions (see enclosed).

Publications

The diversity of ongoing projects is reflected in heteroge-neity of publication topics. Therefore, we grouped the publi-cations according to 3 major themes and we also mentionother publications which are result of cooperation withother Departments at the School of Medicine and ClinicalHospital Center Zagreb. So, for year 2000 to 2003 we did notinclude all groups from collaborative project, since the col-laborative project started towards the end of 2003. How-ever, in the list of publications for 2003 – 2004 period weadded publications of groups recently jointed to the collabo-rative program projekt (grups of Kuva~i}, [kreblin, Bari{i},

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Bari} and Pe}ina-[laus). On the other hand, group of Dr.Peri~i} is no longer in the program of the Institute and is notincluded in the list of publications from 2002 onwards. Seeenclosed lists of publications for periods: 1997-2001, 2002,2003 and 2004.

NEW LABORATORIESESTABLISHEDDURING 2000 - 2004

Laboratory for Confocal MicroscopyLaboraboratory for In Situ HybridizationLaboratory for Cell CulturesAnimal Care FacilityLaboratory for NeurooncologyLaboratory for Non-verbal CommunicationLaboratory for Cognitive Psychology

At this moment, we are developing neurophysiology Labo-ratory for neurophysiology and Laboratory for organotypicslices, as well as Functional Neuroimaging Center at the Uni-versity level (we already have a structural MRI unit).

EDUCATION & TRAINING OF YOUNG INVESTIGATORSAND RESEARCH STAFF

Neurophysiology: (Milan Rado{ – McGill University, Mon-treal; Aleksandra Sin|i} – Max Planck Institute, Frankfurt;Mario Vuk{i} – Goethe Unversity, Frankfurt)

Molecular neurobiology: (@eljka Krsnik – Yale University;Mladen Roko-Ra{in – Yale University)

Developmental neuroscience: Zdravko Petanjek (INSERM,Marseille); Nata{a Jovanov-Milo{evi} (Friedrich Schiller Univer-sity, Jena)

Neurochemistry: Marija Heffer-Lauc (The Johns HopkinsUniversity);

Electron microscopy: Tatjana Belovari (Department ofAnatomy, University of Oslo), Mladen-Roko Ra{in (Institutefor Experimental Physiology, Budapest).

Neuropharmacology: Melita [alkovi}-Petri{i} (Departmentof Neurochemistry, Clinics for Psychiatry and Psychotherapy,University of Wuerzburg, Germany)

AWARDED INTERNATIONAL GRANTS:

Hrvoje Banfi}: Lipid signaling in the cell nucleus» (FIRCAproject)

Neven Henigsberg: Genome-based therapeutic drugs fordepression (GENDEP) – Sixth Framework Programme

Sre}ko Gajovi}: Expression and function of nucleolar pro-tein 1 (Nol1) in mouse (ICGEB Project)

Melita [alkovi}-Petri{i}: Molecular targets of betacytoto-xic drugs within the brain (Deutscher Academischer Aus-tauschdienst – DAAD; research stays and study visits for uni-versity academics and scientists).

Melita [alkovi}-Petri{i}: Collaborative project (DAAD) Ger-many – Bosnia & Herzegovina & Croatia: «Experimental mod-els of Alzheimer's disease and cerebral diabetes related disor-ders» (approved 2004)

Nina Canki-Klain: Programme ECO-NET 2004 (CNRS, Ge-nethon UMR8115, Evry, France)

Nina Canki-Klain: Bilateral COGITO 2004 project (with IN-SERM, Institute de Myologie, Hopital de las Salpetriere, Paris)

Goran [imi}: Bilateral ALIS British Council project 2001-2004(with North East Wales Institute, Wrexham, U.K.)

PENDING APPLICATIONS FOR INTERNATIONALGRANTS:

Sre}ko Gajovi}: Brain Damage and Repair (BRADAREP) –Sixth Framework Programme

Ivica Kostovi}: Protection of developing cortical networks(PRODECONE) – Sixth Framework Programme

TEACHING:

1. Development of PhD Doctoral Study Program (Direc-tion: Neuroscience) within the Doctor of Science DegreeProgram Biomedicine & Health (all members of theBoard have their own course).

2. Initiation of the Doctor of Science - PhD Program in Neu-roscience at the University level;

3. Participation in the interdisciplinary Doctor of Science -PhD Program «Language Communication and Neurosci-ence» at the University level.

4. MD Program – Basic Neuroscience Course at the Schoolof Medicine, University of Zagreb; the first online text-book of neuroscience at the School of Medicine. Intro-duced neurophysiology teaching software «Neurons inAction»; among the top 1% of Chairs at the School ofMedicine, based on results of student evaluations.

PARTICIPATION IN INTERNATIONAL EDUCATION,TRAINING AND COOPERATION PROGRAMS –IN ORGANIZATION OF THE C.I.B.R.:

1.FENS/IBRO International Summer School «Developmentand Plasticity of the Human Cerebral Cortex», Dubrovnik -Zagreb 2003 (with participants from 17 countries).

2. COST B10: Brain Damage Repair, WG2: Regenerationand Functional recovery: Scientific Session to Preparethe Final COST ACTION B10 Workshop (Zagreb, April 23,2004)

3. International Course «Molecular Biology of the AgingNervous System», Dubrovnik, July 26th – July 31st, 2002.

4. Third International Symposium on Normal and Abnor-mal Development of the Human Fetal Brain, Zagreb,Croatia, June 13-15, 2003.

5. The EMBO Practical Course «Anatomy and Embryologyof the Mouse», September 15-22, 2002.

INVITED LECTURERS AT THE CIBR

2004

Glenn E. Morris (U.K.): The molecular defect in spinalmuscular atrophy and prospects for therapy (May 6, 2004)

Mijna Hadders-Algra (Netherlands): Development of pos-tural control: effect of age, brain lesion and preterm birth(March 25, 2004).

Thomas H. Deller (Germany): Lesion-induced anatomicalplasticity in the hippocampus (March 02, 2004)

2003

Bozena Kaminska (Poland): Molecular mechanisms ofthe neuroprotective effect of immunosupressants in focalischemia (June 17, 2003).

Leszek Kaczmarek (Poland): From c-Fos to matrix metal-loproteinases (June 17, 2003)

Zsofia Magloczky (Hungary): Epileptic reorganization inhippocampal formation of human temporal lobe epilepsypatients: sclerosis and progression» (February 27, 2003)

Lucia Wittner (Hungary): Changes in perisomatic anddendritic inhibition in the human epileptic hippocampus(February 27, 2003).

2002

Tamas Freund (Hungary): unctional diversity of inhibitorycircuits in the hippocampus, their involvement in epilepto-genesis and cannabinoid actions (June 13, 2002)

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Margit Kerestesz (Hungary): How could adhesion affectthe behavior of neutrophils? – The role of major F-actin-bind-ing membrane proteins (June 28, 2002)

Dieter B. Wildenauer (Germany): Searching for molecu-lar causes in schizophrenia: from linkage to candidate genes(December 13, 2002)

2001

Glenn E. Morris (U.K.): Emery-Dreifuss muscular distrophy(May 6, 2001)

Milivoj Veli~kovi}-Perat (Slovenia): Team-approach to di-agnostics and treatment of children with cerebral palsy andthe role of parents (December 13, 2001)

David Rowe (USA): An integrated strategy for gene ther-apy for osteogenesis imperfecta (September 10, 2001)

Antonio Bedalov (USA): Chemical genetics – how to dis-cover new cancer treatment (September 21, 2001)

Mitja Peru{ (Slovenia): Attractor theory of recognition andmemory – simulations (December 7, 2001)

COOPERATION WITH CLINICAL PROJECTS

Cooperation on: developmental and perinatal disorders ofthe central nervous system; neuroimaging; neurobiology ofAlzheimer's disease; neurobiology of depression and schizo-phrenia.

Clinical Hospital center Zagreb - Imaging Center, Center forResearch on Perinatal Origins of Neurological and CognitiveDisorders; Academy for Developmental Rehabilitation.

PUBLIC RELATIONS & PROMOTIONOF NEUROSCIENCE

The Croatian Society for Neuroscience (CSFN) was foundedin December 2000 and its seat is at CIBR. The first president(three-year term) was Professor Emeritus Marin Bulat, andthe current president is Professor Ivica Kostovi}. The re-

searchers at the CIBR represent a large portion of CSFN mem-bership, as well as most members of the CSFN's ExecutiveBoard. The CSFN was accepted as an affiliated member ofFENS and IBRO in 2002. The CSFN has successfully organizedFirst Croatian Meeting of Neuroscience (November 2003). Inaddition, the CSFN has organized three consecutive and ex-tremely successful «Brain Awareness Weeks in Croatia» (2002,2003 and 2004): with more than 60 major events each year,the activity was coordinated at the national level (CIBR andCSFN as main organizers, participants from all clinical hospi-tals and Schools of Medicine in Croatia – Osijek, Rijeka, Splitand Zagreb) in addition to numerous lectures and media pre-sentations delivered by CSFN members, more than 1000 pu-pils from primary, secondary and high school have visited theCIBR. As a result, the CSFN has became a member of the«Dana Alliance for Brain Initiatives» in USA and «EuropeanDana Alliance & Brain Campaign», and in 2004 was awardedfor promotion of health (Croatian «Ekspertiza» Award).

PROJECTS WITHIN THE COLLABORATIVE PROJECT ENTITLED «DEVELOPMENT,PLASTICITY, AND REPAIR OF BRAIN AFTER PERINATAL LESIONS»

ETIOLOGY & PATHOPHYSIOLOGY:

1. Ivan Kuva~i}: Factors of preterm birth2. Snje`ana [kreblin-Ku~i}: Influence of antenatal events

on long term neonatal outcome3. Aida Salihagi}-Kadi}: Fetal hypoxia index in prevention

of brain damage

STRUCTURAL AND CHEMICAL REORGANIZATION:

1. Ivica Kostovi}: Development and plasticity of the hu-man frontal lobe

2. Milo{ Juda{: Zagreb Neuroembryological Collection3. Bo`o Kru{lin: Developmental neuropathology of ge-

netic malformations of the human cerebral cortex4. Marija Heffer-Lauc: The role of gangliozides in brain

maturation and plasticity5. Svjetlana Kalanj-Bognar: Glycosphingolipids in brain

development, ageing and neurodegeneration6. Marijan Klarica: Pathophysiology of the cerebrospinal

fluid and intracranial pressure7. Darko Ore{kovi}: Hydrodynamics of the cerebrospinal

fluid8. Davor Je`ek: Neuroendocrine origin of Leydig cells

NEURODEVELOPMENTAL AND COGNITIVE OUTCOME:

1. Vlatka Meja{ki-Bo{njak: Perinatal brain damage in chil-dren with pathological feto-placental doppler

2. Marta Ljube{i}: Communication and language devel-opment in children with early brain lesions

3. Milo{ Juda{ i Marko Rado{: 3D-volume rendering ofMR images of developing human brain

4. Nina Bari{i}: Neuromuscular disorders in children

MOLECULAR MECHANISMS:

1. Ljiljana Kostovi}-Kne`evi}: Determination of gene func-tion in mouse nervous system

2. Sre}ko Gajovi}: Expression and function of nucleolarprotein 1 (Nol1) in mouse

3. Goran [imi}: Reactivation of fetal plasticity in Alzhei-mer's disease

4. Lukrecija Bre~evi}: Cryptic chromosomal rearrangementsand mental retardation

5. Neven Henigsberg: Predictive role of heredity on thera-peutic outcome in psychoses treatment

6. Branimir Jernej: Molecular pathophysiology of sero-tonergic transmission

7. Mary Sopta: Transcriptional regulation in eukaryotes

Poster session at the 1st Croatian Congress of Neuroanatomy

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8. Hrvoje Banfi}: Inositol lipid second messengers in thecell nucleus

9. Ivo Bari}: Inherited metabolic and monogenetic disor-ders in children

10. Nives Pe}ina-[laus: Role of wnt signaling in humancarcinogenesis

INTERNATIONAL SCIENTIFIC COLLABORATION

1. Cooperation with a number of institutions as anextension of European program COST B10 «BrainDamage Repair» (Professor Roland Pochet, ProfessorJose Maria Delgado-Garcia, Sre}ko Gajovi}, BranimirJernej, Milo{ Juda{) – Molecular mechanisms ofneuronal degeneration and regeneration

2. Initial cooperation with Professor Giorgio M. Innocenti(Karolinska Institute, Sweden), Professor PhilippeEvrard (Paris), Professor Heiko Luhmann (Mainz) in theproject «Protection of Developing Neural Networks»(PRODECONE) – Ivica Kostovi}, CIBR

3. Croatian-French research collaboration within theEuropean program «COGITO» (Yehezkel Ben-Ari andMonique Esclapez, INSERM, Marseille - ZdravkoPetanjek, CIBR)

4. Expression and function of nucleolar protein 1 (Nol1)in mouse (Sre}ko Gajovi}, CIBR – ICGEB Trieste)

5. Cooperation with United States through FIRCA project(Hrvoje Banfi}, CIBR)

6. Collaborative project with Department of Neurobio-logy, Yale University School of Medicine (Ivica Kostovi}– Pasko Rakic)

7. Collaborative project with Department of Neurobio-logy, Yale University (Milo{ Juda{ – Nenad [estan iMladen-Roko Ra{in)

8. Collaborative project with Institute of ExperimentalMedicine, Budapest (Milo{ Juda{ and Mladen-RokoRa{in, CIBR – Tamas Freund and Zsofia Magloczka,Hungary)

9. Collaborative project with Neurobiology of AgingLaboratories and Fishberg Research Center for Neuro-biology, Department of Geriatrics and AdultDevelopment, and Department of Ophthalmology, Mt.Sinai School of Medicine, New York (Goran [imi} –Patrick Hoff) and Albert Einstein College of Medicine,Laboratory for Alzheimer’s desease, New York (Goran[imi} – Peter Davies)

10. Collaborative project with Institut für Humangenetik,Erlangen (Thomas Liehr, Erlangen - Lukrecija Bre~evi},CIBR)

11. Collaborative project with Department ofPharmacology and Neuroscience, The Johns HopkinsUniversity School of Medicine (Ronald Schnaar, USA -Marija Heffer-Lauc, CIBR)

12. Collaborative project with The Netherlands Institutefor Brain Research (Ivica Kostovi} and Zdravko Peta-njek, CIBR – Harry B.M. Uylings, Amsterdam)

13. Collaborative project with Karolinska Institute i Hu-ddinge Brain Bank, Stockholm, Sweden (Zdravko Peta-njek i Ivica Kostovi} – Bengt Winblad i Nenad Bogda-novi})

14. Collaborative project with Institute for Physics & Bio-physics, University of Münster (Svjetlana Kalanj-Bog-nar, CIBR)

15. Croatian – Slovenian bilateral project (Davor Je`ek)16. Cooperation with IBRO, FENS and EMBO.17. Cooperation with DANA Alliance for Brain Initiatives

(U.S.A. and Europe)18. Cooperation in neurophysiology, teaching & education

with McGill University, Montreal (Ante L. Padjen andKre{imir Krnjevi})

LIST OF OTHER INTRAMURAL PROJECTS

1. Sre}ko Gajovi}: Expression in function of Nol1 gene inmouse (ICGEB Triest project)

2. Rudolf Gregurek: Experimental development of theCroatian model of psychotherapy

3. Vera Folnegovi}-[malc: Functional psychoses as noso-logical entity

4. Niko Zurak: Apoptosis and neuronal growth factors inmultiple sclerosis

5. Maja Relja: Clinical pharmacology of movement disor-ders

6. Jospi Paladino: Functional neurosurgery7. Selma Supek: Functional organization of the human vi-

sual cortex as revealed by magnetoencephalography(MEG)

8. Rajka Li{~i}: Dementia: electrophysiological and ge-netic study

9. Bojan Ivan~evi}: Influence of high energy ultrasoundon tissue

10. Marijan Klarica: Neurosurgical endoscopic contact ul-trasound probe-knife

11. Stjepan Gamulin: Molecular mechanisms of cell-injuryby energy deprivation

12. Juraj Geber: Neurobiology of benzodiazepine addic-tion

13. Nina Canki-Klain: Genetic and epidemiological study ofmuscle distrophies in Croatia

14. Zdravko Lackovi}: Mitogenic neurotransmitters in vivo15. Melita [alkovi}-Petri{i}: Central nervous system and di-

abetes mellitus16. Ana Maru{i}: Molecular interactions between bone

and immune system

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International Scientific BoardYEHEZKEL BEN-ARI, PhD, Professor & Director,Institut de Neurobiologie de la Méditerranée (INMED)INSERM U29Parc Scientifique de Luminy BP 13,13273 Marseille Cedex 09, France,Tel.: +33 (491) 82 8100;Fax: +33 (4 91) 82 8101E-mail: ben-ariºinmed.univ-mrs.fr or

ben-ariºluminy.univ-mrs.fr

JACK DIAMOND, PhD, Professor,Biomedical Sciences, McMaster University,1200 Main Street West, Hamilton, ON L8N3Z5, Canada,Phone: (905) 525-9140 ext. 22222Fax: (905) 522-8804E-mail: diamondºfhs.csu.McMaster.CA

MIRKO DIKSIC, PhD, Professor,Department of Neurology & Neurosurgery,Montreal Neurological Institute, McGill University,3801 University Street, Montreal QC H3A 2B4, CanadaPhone: (514) 398-8526E-mail: mirkoºpet.mni.mcgill.ca

PEDRO A. FERCHMIN, PhD, Professor,Department of Biochemistry,University Central Del Caribe School of Medicine,Call Box 60-327, Bayamon 00960-6032, Puerto RicoPhone: (787) 786-6285Fax: (787) 786-6285E-mail: ferchminºcoqui.net

KRE[IMIR KRNJEVI], PhD, Professor,Anesthesia Research Department,McIntyre Medical Sciences Building, McGill University,3655 Drummond Street, Montreal, QC H3G 1Y6, CanadaPhone: 514-398-6001Fax: 514-398-4376E-mail: krnjevicºmed.mcgill.ca

ANTE L. PADJEN, MD, DSc, Professor,Department of Pharmacology & Therapeutics, McGill University,3655 Sir William Osler Promenade,Montreal, Quebec, Canada H3G 1Y6Phone: (514) 398 3603Fax: (514) 398 4449 or 398 6690E-mail: ante-padjenºmcgill.ca or alpºpharma.mcgill.cahttp:// www.alp.mcgill.ca

PASKO RAKIC, MD, DSc, Professor & Director,Doctor honoris causae – University of Zagreb & Member ofHAZU,Department of Neurobiology,Yale University School of Medicine,333 Cedar Street, New Haven, CT 06510Phone: 203-785-5288Fax: 203-785-5263E-mail: pasko.rakicºyale.edu

MIRJANA RANDIC, MD, PhD, ProfessorDepartment of Biomedical Sciences,Iowa State University,Ames, IA 50011,Phone: 515-294-7793Fax: 515-294-2315E-mail: mrandicºiastate.edu

HARRY B.M. UYLINGS, PhD, Professor,University of Amsterdam and The Netherlands Institute forBrain ResearchMeibergdreef 33, 1105 AZ Amsterdam, The NetherlandsPhone: 31 (20) 566 5521 or 31 (20) 566 5500Fax: 31 (20) 696 1006E-mail: H.Uylingsºnih.knaw.nl

DICK F. SWAAB, MD, DSc, Professor & Director,The Member of the Netherlands Academy of Arts & Sciences,The Netherlands Institute for Brain Research,Meibergdreef 33, 1105 AZ Amsterdam, The NetherlandsE-mail: infoºnih.knaw.nl

BENGT WINBLAD, MD, PhD, Professor & Director,Karolinska Institute, Novum plan 4, Geriatric section B84,171 77 Huddinge, Stockholm, SwedenE-mail: Bengt.Winbladºneurotec.ki.seE-mail: b.winblad.kaspacºneurotec.ki.sehttp://info.ki.se/index_en.html

PHILIPPE EVRARD, MD, DSc, Professor and Chief,Service of Pediatric Neurology and Metabolic DiseasesDirector, INSERM E9935Université Paris 7 Denis-Diderot (Faculté de MédecineXavier-Bichat)Hopital Robert-Debré (AP-HP)48 Boulevard SérurierF-75019 Paris, FranceE-mail: philippe.evrardºrdb.ap-hop-paris.frURL: http://www.pediatric-neurology-paris.org

TAMAS F. FREUND, PhD, DSc, Professor & Director,Institute of Experimental Medicine, Hungarian Academy ofSciences,Budapest 8, Szigony u. 43, H-1083 Hungary,Phone: +36 (1) 210-9410 or 210-9400/ext. 244Fax: +36 (1) 210-9412E-mail: freundºkoki.hu

GIORGIO M. INNOCENTI, Professor & Director,Division of Neuroanatomy and Brain Development,Department of Neuroscience,Karolinska Institutet Doktorsringen 12,Retzius väg 8, S-17177 StockholmPhone: +468-7287862Fax +468-315782E-mail: Giorgio.Innocentiºneuro.ki.se

OLEG A. KRISHTAL, Professor,Member of Academia Europea, Member of UkrainianAcademy of Sciences,Corresponding Member of the Russian Academy of Sciences,Bogomoletz Institute of Physiology, Department of CellularMembranology,Bogomoletz St. 4, Kyev 01024, UkrainePhone: +380 44 253 24 66 (office); +380 44 257 91 50 (home)Fax: +380 44 256 25 90E-mail: krishtalºserv.biph.kiev.uahttp://www.biph.kiev.ua/�krishtal

ROLAND POCHET, MD, DSc, Professor & Director,ULB, Laboratoire d'Histopatologie,Route de Lennik, 808,B-1070 Bruxelles,Phone: +32 (2) 555-6374 / 6287Fax: +32 (2) 555-6285E-mail: rpochetºulb.ac.be

RONALD L. SCHNAAR, PhD, Professor & Chairman,Departments of Pharmacology and Neuroscience,The Johns Hopkins University School of Medicine,725 N Wolfe St., Baltimore, MD 21205Phone: (410)-955-8392Fax: 410-955-3023E-mail: schnaarºjhu.edu

NENAD SESTAN, MD, PhD, Professor,Department of Neurobiology,Yale University School of Medicine,333 Cedar Street, SHM C-310, New Haven, CT 06510Phone: (203) 737-2190Fax: (203) 785-5263E-mail: nenad.sestanºyale.edu

conferences

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conferences mef.hr

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Brain Awereness Week(14 – 20 March 2005)

During the Brain Awereness Week(BAW) wide public is being introducedto the actual problems of neuroscience,with the causes, amplitude and con-sequences of neurological and psycho-logical diseases, as well as with thepossibilities of diagnostics, preventionand cure of these diseases. In just threeyears BAW in Croatia grew up into realfestival of neuroscience. Increasing num-ber of institutions and experts is givinga contribution in organizational andeducational sense. From the modestbeginning in 2002 with just 25 expertsparticipated organizing 22 events,mostly in Zagreb, we came to thenumber of 125 experts helding 80events throughout Croatia. Regardingthose data, Croatia is in the world's topand if we make some kind of com-parison (on example: size of thecountry, number of scientific and edu-cational institution, number of clinicsand hospitals) then we are on the top.

We organized series of public lectu-res, stands, consultations and work-shops. During the BAW, specialattention is dedicated to the educationof jovenails. In three years of BAW morethan 1000 pupils and students passedthroughout CIBR. We organizedpopular lectures and workshops forthem, as well as sightseeing of our labs.

Last year BAW in Croatia gave thespecial accent on four topics: 1. Recentadvances and challenges in brain re-search, 2. Brain and hormones, 3. Birthand death of neurons and 4. Depres-sion. Beside these topics, it was drawnattention to many current themes likethe effects of alcohol and drugs onbrain, epilepsy, autism and migraine.We had 48 events all-around Zagreb,with more than 2000 people attendedthose events. In Split, Rijeka, Osijek,Dubrovnik, Cakovec we had 31 eventswith more than 1000 people attendedthem.

On CIBR we had a few very attractivelectures. Associated professor Sre}koGajovi}, Ph.D. and professor Milo{Juda{ Ph.D., organized a public stand“Birth and death of neurons”. Thetheme of Sre}ko Gajovi} was “From theembryonic cells to neurons” and theone of Milo{ Juda{ was “Neural stemcells: basic research and possibilities ofthe clinical application”. One of thescientific priorities in this century arethe stem cells. Investigations of neuralstem cells are very important for thenormal development of central nervoussystem witch could lead us to the newtherapies for neurological diseases andinjuries of nervous system (combina-

tion of genetic engineering andreplacing therapy with the neural stemcells). “New attains and challenges inbrain research”, lecture held byradiologist Marko Rado{, Ph.D. was abig hit where he talked about thedifferent intensity of activation in theregions of man and woman brain dueto different kind of stimulation. Brainand hormones topic involved threelectures for the students: associatedprofessor Goran [imi}, Ph.D. wastalking about “Stress and hormones”,Elizabeta Radoni} M.Sc. about “Estro-gen and brain” and associatedprofessor Svjetlana Kalanj-Bognar,Ph.D. about “Neurosteroids”. Lecturesand workshops for the pupils were heldby @eljka Krsnik, M.Sc., Nata{aJovanov-Milo{evi}, M.Sc., Milan Rado{,M.Sc. and associated professor ZdravkoPetanjek, Ph.D.

This years topics are: 1. Autism, 2.Europe and brain research and 3.Recent advances and challenges inbrain research. We hope that we’llmanage to reach to even greaternumber of people this year. This is themain priority of BAW 2005.

Kristina Grbi}

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First Croatian Congressof NeuroscienceZagreb, 21.- 22. November 2003.

The Croatian Society for Neurosci-ence (CSFN) is a recently founded soci-ety dedicated to educating and inform-ing its members and the general publicin Croatia about the results and impli-cations of research relating to the ner-vous system. For a small country withlimited budget resources it is difficultto stimulate and finance large-scale

productive and novel research in thisimportant area of basic and clinical sci-ences.

Since the major mission of our soci-ety is to inform the public about theprogress and benefits of neuroscienceresearch, from 21th to 22th November2003, CSFN has organized the First Cro-atian Congress of Neuroscience with a

basic goal to get together basic andclinical neuroscientists to demonstratethe topics of their current research. Toaccomplish this goal, presentationswere restricted to the research done inCroatian laboratories and clinics.

The congress was subdivided in threedistinct symposia that focused on thefollowing topics:

• Hydrocephalus research,

• Brain damage and repair and

• Evolution of human brain and be-havior.

These topics attracted many differentresearch groups, beginning with ex-perts in molecular biology, cognitiveneuroscience, clinicians in the field ofneurology, psychiatry and neurosur-gery, and finaly, basic neuroscientistsfrom all four Schools of Medicine inCroatia, Croatian institute for brain re-search and research institutions like theInstutute «Ru|er Bo{kovi}».

The plenary part of the Congress washeld at the School of Medicine, whileposters were presented at the Croatianinstitute for brain research. All presen-tations (71 poster presentations and 14lectures) were published in the Book ofabstracts, as a special edition of in-dexed journal Neurologia Croatica.

Specific for this congress was the at-tendance of a large number of expertsin different fields of modern neurosci-ence, e.g. biomedicine, psychology, lin-guistics, speech-pathology, sociologyand many others.

Since connecting Croatian neuro-scientists is one of the most importantgoals of CIBR from its foundation, it isimportant to emphasize that the con-gress was a confirmation of this goalgetting fulfilled through collaborationof these groups in many research pro-jects, as well as graduate and postgrad-uate teaching.

We believe that only through inte-grating both clinical and basic neuro-science, can the position of Croatianneuroscience in modern neurosciencebe guaranteed.

Goran Ivki}and Elizabeta Radoni}

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IBRO/FENSInternational Summer School 2003

The Summer School, sponsored byIBRO and FENS, was held at the Interna-tional Center of Croatian Universities(ICCU) in Dubrovnik (invited lectures)and the second part (practical tutorials)was held in laboratories of the CroatianInstitute for Brain Research (CIBR) inZagreb from 20th September - 4th Oc-tober, 2003.

The course was intended for ad-vanced Ph.D. students or post-docs inneuroscience and related fields fromboth Western Europe and IBRO-CEERCRegion, as well as from other IBRO re-gions. From 61 applications, a total of26 students from 15 countries were ac-cepted: Hungary (3), Romania (1),Georgia (1), UK (1), USA (1), Sweden(1), Russia (4) , Croatia (3), Germany(2), Poland (2), Finland (2), Czech R (1),Iran (1), India (1), France (2).

Invited speakers were eminent neu-roscientists: Giorgio Innocenti andTorkel Klingberg, Karolinska Institute,Stockholm; Ante Padjen, McGill Univer-sity, Montreal; Catherine Verney andPhilippe Evrard, INSERM Paris; Yeheze-kel Ben-Ari and Monique Esclapez IN-SERM Marseille; Harry B.M. Uylings,University of Amsterdam and The Neth-erlands Institute for Brain Research;Joan Stiles, University of California, SanDiego; Tamas F. Freund , Institute forExperimental Medicine - Hungarian Aca-demy of Sciences, Budapest; Milos Ju-das and Ivica Kostovic, Croatian Insti-tute for Brain Research, Zagreb.

Summer school included followingtopics: neurogenetic events in the hu-man cerebral cortex - proliferation, mi-gration and cell lineages; synaptoge-nesis, development of dendrites andformation of thalamocortical, cortico-cortical and monoaminergic connec-tions; genetic and molecular mecha-nisms of cortical areal specification;early cortical activity, development andplasticity of hippocampal circuitry andsignaling molecules; development ofworking memory and executive func-tions in non-human primates and nor-mal and dyslexic children; neuroima-ging of cortical development; vulnera-ble developmental windows in corticaldevelopment; neuroprotection in earlylife; plasticity, recovery, repair of cortexand neurodevelopmental outcome af-ter perinatal damage; neuroprotectionin early life; generic vs. species-specific

features of human neocortical evolu-tion.

Practical courses (conducted byCIBR's faculty) held from 28th Septem-ber to 4th October, 2003 in laborato-ries of the Croatian Institute for BrainResearch (CIBR) in Zagreb included:MRI Structure of the Cerebral Cortex;MRI and other Neuroimaging methods(fMRI, MEG, SPECT); 3D-Structure ofthe Human Cortex revealed on HumanBrain Preparations; Stereological Analy-

sis of Cortex with Neurolucida andStereoinvestigator Systems; Multipleimmunocytochemical labeling tech-niques; In situ hybridization; Electronmicroscopy; Confocal microscopy; Iso-lation and staging of Mammalian Em-bryos; Tracing of Neural Pathways inHuman Cortex (DiI etc.); LaboratoryTests of Cognitive Function in Children;Video-monitoring of Preverbal Com-munication.

Milo{ Juda{

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Section for DevelopmentalNeuroscience

Head: Milo{ Juda{, M.D., D.Sc.,Associate Professor of Neuroscience & Anatomy,mjudasºhiim.hr

Members: Ivica Kostovi}, M.D., D.Sc., Professor of Neuroscience & Anatomy; ZdravkoPetanjek, M.D., D.Sc., Assistant Professor of Neuroscience & Anatomy; Goran[imi}, M.D., D.Sc., Assistant Professor of Neuroscience & Anatomy; MarioVuk{i}, M.D., M.Sc., Research Assistant in Neuroscience; Mladen-Roko Ra{in,M.D., Research Assistant in Neuroscience; Nata{a Jovanov-Milo{evi}, V.D.,M.Sc., Research Assistant in Neuroscience; @eljka Krsnik, B.B.Sc., ResearchAssistant in Neuroscience; Kristina Grbi}, B.B.Sc., Research Assistant inNeuroscience; Technicians: Zdenka Cmuk, Danica Budin{}ak, Bo`ica Popovi},and Maja Horvat. Graduate students: Dra`en A`man, Dora Anzulovi}, AlenBabacanli, Raphael Bene, Dunja Gorup, Pero Hraba~, Petra Nimac, AlenPajtak, Mihovil Pletikos, Sini{a Rogini}, Goran Sedmak, Lana Vasung.

Researchers at the Section for Developmental Neuroscience pursue several related lines of research, and current projects of fourteams are described in separate leaflets (see: Laboratory for Neurohistology and Chemical Neuroanatomy – I. Kostovi}; Labora-tory for Neuromorphometry – Z. Petanjek; Laboratory for Developmental Neuropathology – G. [imi}; and Confocal MicroscopyUnit – N. Jovanov-Milo{evi}). These research teams together investigate the following research topics: Collaborative researchproject entitled «Development, Plasticity, and Repair of Brain After Perinatal Lesions»; Immunofluorescen mono- and multi-labeling organotypic slice culture (GFP transfection); the application of 3-D neuron reconstruction in confocal microscopy (reor-ganisation of the Fascia dentata after entorhinal lesion in EGFP-transgenic mouse); Specific protein determination and charac-terization of the cells of the subventricular zone; Origin, migration and maturation of GABAergic cortical interneurons; Normaland abnormal development of human and primate cerebral cortex; The study of tau protein phosphorylation during develop-ment and neurodegenerative disease; The role of SMN protein in apoptotic cell death and abnormal migration of motor neu-rons in pathogenesis of spinal muscular atrophy; Monoclonal antibody studies of dopamine receptors in human and rodentbrain and neuronal cell cultures. These four teams also have an established international cooperation with: Professor Harry B.M.Uylings (The Netherlands Institute for Brain Research), Professor Nenad Bogdanovi} (Karolinska Institute, Sweden), Dr. L. Groc(CNRS-UMR 5091, Bordeaux, France), Dr. Monique Esclapez (INMED-INSERM U29, Marseille, France), Professor Thomas Deller(Department of Clinical Neuroanatomy, Goethe University, Frankfurt a.M., Germany).In addition, projects led by dr. Juda{ are currently focused on the following topics:1. Developmental neuropathology of cortical malformations and neuronal migration disorders (holoprosencephaly, Wal-

ker-Warburg syndrome);2. Prenatal development of nitrinergic neurons in the human basal forebrain and basal ganglia;3. Comparative analysis of NOS1-expression and co-localized genes and transcription factors in pyramidal neurons of human, rhe-

sus monkey and mouse frontal cortex (Milo{ Juda{ & Mladen-Roko Ra{in - in collaboration with Department of Neurobiology,Yale University School of Medicine – Laboratory of Dr. Nenad [estan), with focus on language-related areas of the frontal lobe;

4. Comparative analysis of FOXP2-expression in developing and adult cerebral cortex of mammals representing most majortaxonomic classes (Mladen-Roko Ra{in & Milo{ Juda{ - in collaboration with Department of Neurobiology, Yale UniversitySchool of Medicine – Laboratory of Dr. Nenad [estan),

5. Molecular and cellular characterization of dominant ataxia with hydrocephalus in the «Clumsy» mutant mouse (@eljkaKrsnik – in collaboration with Dr. Nenad [estan's laboratory).

6. Correlated MRI-histological studies of normal and disturbed prenatal development of the human telencephalon (in collab-oration with Marko Rado{, M.D., D.Sc., neuroradiologist, Section for Neuroimaging), and correlated quantitativeMRI-histological analysis of telencephalon in humans, anthropoid apes (chimpanzee, bonobo, gorilla), and rhesus mon-keys (in collaboration with Section for Neuroimaging and Laboratory of Dr. Nenad [estan).

Selected publications (see also separate leaflets for above mentioned laboratories):Juda{ M, [estan N, Kostovi} I (1999) Microscopy Research and Technique 45(6):401-419.Kostovi} I, Juda{ M (2002) The Anatomical Record 267:1-6.Kostovi} I, Juda{ M, Rado{ M, Hraba~ P (2002) Cerebral Cortex 12:536-544.Juda{ M, Ra{in MR, Kru{lin B, Kostovi} K, Juki} D, Petanjek Z, Kostovi} I (2003) Brain & Development 25:32-39.Juda{ M, Jovanov-Milo{evi} N, Ra{in MR, Heffer-Lauc M, Kostovi} I (2003) Progress in Molecular and Subcellular Biology 32:1-32.Juda{ M, Rado{ M, Jovanov-Milo{evi} N, Hraba~ P, [tern-Padovan R, Kostovi} I (2005) American Journal of Neuroradiology (in press).

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Croatian Institute for brain researchURL: http://www.hiim.hr

Laboratory for Neurohistologyand Chemical NeuroanatomySection of Developmental Neuroscience

Head: Ivica Kostovic, MD, Dsc.Profesor of NeuroscienceDirector of CIBR, ikostovºhiim.hr

Collaborator: Milos Judas, MD, PhD.,Associate Profesor of NeuroscienceHead of Section of Developmental Neuroscience,mjudasºhiim.hr

Members: Roko Mladen Rasin, MD.Zdenka Cmuk, lab. ing.Danica Budinscak, lab. ing.Bozica Popovic, lab. ing.Maja Horvat, lab. ing.

Collaborative research project:

DEVELOPMENT, PLASTICITY, AND REPAIROF BRAIN AFTER PERINATAL LESIONSHistochemistry and immunohistochemistry are very useful methods indevelopmental neuroanatomy research, especially in research of hu-man brain development. In this laboratory following methods are per-formed:

– Golgi and byocitin methods for staining of whole single neuron,– histochemical methods for growing fibers

(AChE, PAS-AB, Gallyas staining),– immunoperoxidase labeling of tissue sections,– immunofluorescent labeling of tissue sections,– immunofluorescent double-labeling of tissue sections.

UNIT FOR NON-RADIOACTIVE IN SITU HYBRIDIZATIONOF HUMAN BRAIN TISSUE

Coordinator: Zeljka Krsnik, mol. biol. ing, MSc.Research Assistant of Neuroscience,zkrsnikºhiim.hr

In situ hybridization techniques allow specific mRNA to bedetected in morphologically preserved tissue section. Incombination with immunocytochemistry, in situ hybridiza-tion might relate microscopic topological information togene activity at the DNA, RNA and protein level.

Selected publicationsKostovic I. et al., Cereb. Cortex 2002.Kostovic I., Judas M., Anat. Rec. 2002.Kostovic I., Judas M., Trends Neurosci. 1991.Kostovic I., Rakic P., J. Comp. Neurol. 1990.Kostovic I., Prog. Brain Res 1990.

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratoryfor NeuromorphometrySection of DevelopmentalNeuroscience

Head: Zdravko Petanjek, MD, Dsc.Assistant Professor of Gross Anatomy and Neurosciencezpetanjekºnet.hr

Tools:

NEURON RECONSTRUCTION STEREOLOGYIn studies of neuron development and pathology, quantitative analysis of total neuron number and individual neuron mor-phology is preferable. In this laboratory methods of neuron reconstruction and stereology are performed. Reconstructionand analysis of three-dimensional branching pattern of the axons and dendrites together with spine counting is performedusing Neurolucida software (Olympus Bx50 microscope connected to Hitachi 3CCD color video camera HV-C20M that dis-plays picture on PC monitor). On the same system optical fractionator method is the most common stereological procedureused in the Stereoinvestigator software package that allows performing other stereological methods too. Parameters of neu-ron reconstruction and stereology are topologically and statistically analyzed.

Research fields:

Normal and abnormal development of humanand primate cortex - specific aims:

– To establish quantitative parameters of dendrite and spine development oflayer IIIC pyramidal neurons of human prefrontal cortex as a model for devel-opment of cognitive circuitry (collaboration Prof. HBM. Uylings, NetherlandsInstitute for Brain Research).

– To establish quantitative parameters, including regional, interindividual andsex differences of cognitive circuitry in adult human cerebral cortex.

– To study disrupted development of cognitive circuitry in Down syndrome, au-tism and schizophrenia.

Experimental models used:– To study effect of enriched environment on neuron morphology in hippo-

campus and cortex of aged rats (collaboration Prof. N. Bogdanovic, Karolin-ska Institute, Sweeden).

– To study effect of in vivo blockage of activity on neuron morphology in rat hippocampal formation during postnatal de-velopment (collaboration Dr. L. Groc, CNRS-UMR 5091, Bordeaux, France).

– To study morpho-functional development of neurons in monkey hippocampal formation (collaboration Dr. M. Esclapez,INMED -INSERM U29, Marseille, France).

– To study interneuron loss in rat experimental model of epilepsy (collaboration Dr. M. Esclapez).

Selected publicationsGroc L., Petanjek Z. et al., Eur. J. Neurosci. 2002, 2003.Dincourt C., Petanjek Z. et al., J. Comp. Neurol. 2003.Judas M. et al., Brain Devel. 2003.

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Confocal Microscopy Unit

Laboratoryfor NeuromorphometryCoordinator: Nata{a Jovanov-Milo{evic, VD, MSc.

Research Assistant of Neurosciencenjovanovºhiim.hr

Tools:

IMMUNOFLUORESCENT MONO AND MULTILABELINGORGANOTIPIC SLICE CULTURE (GFP TRANSFECTION)

– Image acquisition with laser confocal microscope (Zeiss, AXIOVERT 220N, 510 LSM META)and digital video camera (Nikon DXM 1200)

Multifluorescence microscopy is a one of crucial tool for studying biological phenomena. Colocalization of fluorescentlylabeled molecules (immunostainings, fluorescent proteins, etc.) may be used in order to analyze structural and chemicalphenotype of neurons and axonal pathways and as the first indicator of functional interaction. Current applications:

– To follow proteins of interest through development, to the level of subcellular orga-nelles, directly and non-invasively,

– To investigate gene expression (using GFP and other fluorescent proteins) in tissuesection,

– To identify agonists and antagonists of specific signal transduction pathways,– For quantitative colocalization analyzes.

Research fields:– Specific protein determination and characterization of the cells of subventricular

zone with special emphasis on their role in development of cortico-cortical connec-tions (collaboration project PRODECONE).

– Origin, migration and maturation of GABAergic cortical interneurons (collaborationDr. M. Esclapez).

– Special reference to human and primate brain development– Importance of disrupted development in epilepsy, schizophrenia and after hi-

poxic-ishemic lesion.

APPLICATION OF 3-D NEURON RECONSTRUCTIONIN CONFOCAL MICROSCOPY

Reorganisation of the Fascia dentata after Entorhinallesion in EGFP-transgenic mouse

Coordinator: Mario Vuk{ic, MD, MSc.Research Assistant of Neurosciencemariovuksicºnet.hr

Approach: 3D reconstruction and analysis of granule cells at differ-ent time points post lesion

Methods: in vivo lesioning of the entorhinal cortex, immunohisto-chemistry, neuromorphometry (3-D reconstruction by means of Neu-rolucida system and confocal module), and confocal microscopy.

Selected publicationsVuksic M. et al., Pediatr. Neurol. 2002.Judas M., Jovanov-Milosevic N. et. al., Prog. Mol. Subcell. Biol. 2003.Jovanov-Milosevic N. et. al., FEBS J. 2005.

Collaboration Prof. T. Deller,Department of Clinical Neuroanatomy,Goethe University, Frankfurt am Main

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Croatian institute for brain researchURL: http://www.hiim.hr

Laboratory for developmentalneuropathologyURL: http://dementia.hiim.hr

Head Goran [imi}, M.D., D.Sc.gsimicºhiim.hr

Members Kristina Grbi}, B.B.Sc.kgrbicºhiim.hr

The main lines of research in my laboratory are currently directed towards:1) the study of tau protein phosphorylation during development and neurodegenerative disease,

2) the role of SMN protein in apoptotic cell death and abnormal migration of motor neurons in pathogenesis of spinal mus-cular atrophy,

3) monoclonal antibody studies of dopamine receptors in human and rodent brain and neuronal cell cultures.

Selected publicationsG. [imi} et al., J. Comp. Neurol. 1997G. [imi} et al., Neuroscience 1999, 2005G. [imi} et al., J. Neuropathol. Exp. Neurol. 2000G. [imi} et al., Exp. Neurol. 2000G. [imi}, Lancet Neurol. 2002G. [imi} et al., Prog. Mol. Subcell. Biol. 2003

Accurate biological analysis of cerebrospinal fluid helps todiscriminate between tau protein types present in physiolog-ical conditions and tau released during the progression of aparticular neurodegenerative disease (Alzheimer's disease,frontotemporal dementia, progressive supranuclear palsy,corticobasal degeneration, hereditary tauopathies).

Electron-microscopic appearance of an anterior horn neuron in a child with spinalmuscular atrophy (the second most common lethal autosomal recessive disease)showing features of both apoptosis (hyperchromatosis of nuclear membrane,segregation of the nucleus into apoptotic bodies) and autophagic degeneration(autophagic vacuoles, arrows). This finding contradicts earlier studies that failedto find such evidence and suggest that blockade of an inappropriate persistenceof normally occurring motor neuron programmed cell death may be a potentialtherapeutic strategy for spinal muscular atrophy.

DRD3 receptor vesicles (green) stained with DRD3 monoclonal antibody againstN-terminus (MANDOP 33). The Golgi apparatus (red) is stained with the rabbit an-tibody against Golgi protein GM130. Cell is counterstained using DAPI (blue).Staining shown by the two antibodies showed no colocalization. Altered do-paminergic signalling pathways have been implicated in the etiology of severalmajor psychiatric and neurologic conditions, including schizophrenia, substanceabuse and Parkinson’s disease.

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Section for Psychopharmacologyand Neurobiology of BehaviourHead: Neven Henigsberg, MD, DSc, Assistant Professor)

Section for Psychopharmacology andNeurobiology of Behaviour is dedicatedto the ethical study and participation indiscovery of new medications for psy-chiatric disorders through clinical re-search. The goals of the Section are tostimulate the quality and quantity ofclinical trials; to streamline the researchprocess, from protocol design to publi-cation; and to educate investigators inGood Clinical Practice, Regulatory Af-fairs and Study Management. CIBR hasestablished Institutional Review Boardpanels to review all proposed researchinvolving human subjects to ensurethat the subjects' rights and welfare areadequately protected.

Section for Psychopharmacology andNeurobiology of Behaviour is a mul-tidisciplinary research group, involved inintegrative neuroscience research intobrain mechanisms of psychiatric disor-ders. Section is responsible for research,education and treatment that includes,but is not limited to, clinical psycho-pharmacology. At present, the CIBR is astimulating academic environment inwhich research and teaching come to-gether to advance knowledge of the-rapeutic opportunities in mental disor-ders. A major strength of the CIBR is thecapacity to study the brain using thecombined perspectives of clinical andbasic research. The congenial researchsetting actively fosters collaborationbetween investigators who have diffe-rent areas of expertise. Over 50 facultymembers contribute their research andclinical strengths to multidisciplinaryteams.

Human studies use behavioral, cogni-tive, neuroimaging and electrophysio-logical methodology.

Organization

Section for Psychopharmacology andNeurobiology of Behaviour is function-ally integrated with the Section forClinical Trials of “Neuron” DiagnosticCentre, which is “in-house” medical in-stitution providing specialists’ servicesin all CNS-related areas.

In addition to their appointments inthe CIBR, the research investigators areaffiliated with university departmentsin other major hospitals.

In order to promote integrative col-laboration between most recognizedinstitutions in clinical research, Sectionis coordinating the “CIBR network ofclinical research”, a multi-partner initia-tive to promote clinical research inCroatia by building up research infra-structure and professional resources,streamlining governance and regula-tory processes. Four leading institu-tions are joined now to this Network,with overall capacity of 2.000 hospitalbeds, representing a considerable po-tential for fast recruitment in trials in al-most any CNS area, aimed to improvespeed, quality and integration of clini-cal research.

Research interestsResearch interests of the Section are

mainly focused to:• recognition of predictors in neu-

robiological and brain imagingparameters of efficacy and safetyof psychoactive drugs;

• participation in development ofgenomic-based therapies in de-pression, schizophrenia and pro-gressive dementias.

As a single clinical site outside the EUcountries, CIBR Section for Psychophar-macology became in 2004 the fullmember of European Commissionfunded (FP6) scientific project “Geno-mic-based therapies for depression/GENDEP/”, involving 12 clinical centersin 9 European countries.

Respecting all ethical principles, scien-tific research in psychiatric genetics isfurther empowered by cooperation withCroatian Public Health Institute, which ismaintaining one of the oldest register ofpsychiatric patients in Europe.

EducationSection participates in provision of

educational programs to undergradu-ate and postgraduate students as wellas continuing medical education groupswhich provide for the optimal utiliza-tion of advances in pharmacologicaltreatment of psychiatric disorders andfor the integrated skills for participa-tion in clinical research.

Cooperation with industryResearchers at the Section have in over

50 multicenter, international clinical

trials studied many novel treatments thathave subsequently been approved for cli-nical use in adult, adolescent, child andgeriatric populations diagnosed with avariety of mental disorders.

Section for Psychopharmacology andNeurobiology of Behaviour is offeringto its partners a variety of services re-lated to regulatory submission of atrial, its conductance and follow-up, in-cluding:

• EC and regulatory authority sub-missions and follow-up,

• development of clinical trial pro-tocols,

• feasibility review of new studies,• educational and training oppor-

tunities for CRAs, clinical investi-gators and coordinators,

• full study conductance and coor-dination,

• complete clinical, laboratory andtechnical support, including spe-cimen preparation, processing anddelivery,

• computerised trial management,• data analysis and production of

individual study reports, andmeta-analyses of clinical trials,

• pharmacoeconomic analyses,• patient education.

Section integrates a Quality Assur-ance Unit, aimed to reinforce full com-pliance with GCP and regulatory re-quirements in conductance of the trial.

Future development

Integration of clinical psychophar-macology with pre-clinical psycho-pharmacology researches is among themajor interests of investigators withinSection. Researchers have extensive ex-perience in early phases of drug devel-opment. The scope of clinical researchat CIBR is widening to early phases ofclinical trials. There are accommoda-tion capacities for 28 subjects, includ-ing central kitchen and rooms for socialactivities.

The aim is also to further strengthenalready existing pharmacogenetic re-search at CIBR with other groups inCroatia, involving leading researchersin psychiatry, molecular genetics, neu-roimaging, anatomy, and molecular bi-ology.

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Project title: Inositol lipidsignalling in the cell nucleiGroup leader: Hrvoje Banfi} MD, PhD,

professor of Neuroscience and Physiology

PLC family comprises twelve isoforms that can be subdivided into five types (�, �, �, � and �) based on their structural differ-ences. The activation of PLCs located in the plasma membrane, in response to hormone binding, has been extensively investi-gated and many aspects of their regulation are now understood. However, evidence has accumulated suggesting the pres-ence of PLCs in the cell nucleus, but little is known about regulation, function and possible subnuclear localization of differ-ent PLC isoforms. Recently we purified PLC from the membrane-depleted rat liver nuclei. About 60% of the total PLC-activitycorresponded to �1b-isoform, 30% to PLC-�1 and less then 10% to PLC-�1. PLC-�1b and �1 were found in the nuclear matrix,while PLC-�1 was detected in the chromatin. Two peaks of increase in the total PLC-activity were detected occurring at 6 h and20 h after partial hepatectomy. An early increase in PLC-�1b-activity in the nuclear matrix was associated with serinephosphorylation of the enzyme, while the later increase paralleled the increase in the amount of protein. The increase in thePLC-�1-activity measured at 6 h and 20 h after partial hepatectomy were associated with tyrosine phosphorylation of the en-zyme. The activity of PLC-�1 and the amount of the protein found in the chromatin was increased only at 20 h after partialhepatectomy.

The large family of phosphoinositide 3-kinase (PI3K) enzymes can be divided into three distinct classes (I, II and III) based onsequence similarity and lipid products they generate in vitro. Whilst biological roles have been assigned to the class I and classIII PI3K enzymes, the significance of class II PI3K enzymes remains elusive. In mammalian cells there are three class II PI3Kisoforms PI3K-C2� PI3K-C2� and PI3K-C2� and they act as downstream targets of growth factor, chemokine and integrin re-ceptors. In Drosophila melanogaster targeted expression of the single class II enzyme modified signalling downstream ofgrowth factor receptors. In addition to their role in acute receptor mediated signalling, PI3K-C2� and PI3K-C2� have alsobeen identified in the nucleus. The specific activity of nuclear PI3K-C2� increased during G2/M phase of the cell cycle?and?this stimulation was dependent upon calpain mediated hydrolysis. On the other hand, during differentiation of the cells nu-clear PI3K-C2� was activated due to tyrosine phosphorylation.In the future work we will: (1) quantify the effects of class II PI3K and PLC isoenzymes overexpression and attenuation of en-dogenous expression by RNAi on cell cycle progression and cell differentiation; (2) characterise the nuclear localization se-quence present in class II PI3K and PLC isoenzymes and establish the mechanism that facilitates transport across the nuclearmembrane; (3) detail the compartmentalisation of class II PI3K enzymes within the nucleus; (4) establish the exact position ofcalpain-mediated cleavage of class II PI3Ks; (5) identify the targets of PtdIns(3)P in the nucleus and (6) identify PKC isoformstranslocation into the nucleus due to activation of different PLC isoforms.

Recent publications:

1. V. Crljen, D. Vi{nji} and H. Banfi}, FEBS Lett. 571: 35-42, 2004.2. V. Crljen, S. Volinia and H. Banfi}, Biochem. J. 365: 791-799, 2002.3. A. Sin|i}, A. Aleksandrova, A.P. Fields, S. Volinia and H. Banfi}, J. Biol. Chem. 276: 17754-17761, 2001.

Lamin B PLC Lamin B + PLC

Immunohistochemical localization of lamin B and PLC in the membrane-depleted nuclei

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratory for NeurochemistryProject leader: Svjetlana Kalanj Bognar, MD, PhDCollaborators: @eljka Vukeli}, PhD; Davor Je`ek, MD, PhD;

Ivana Fura~, BScThe main interests of the project: Glycosphingolipids in brain development, aging andneurodegeneration realised within the Laboratory for neurochemistry:

(1) analysis of glycosphingolipid structures in brain tissue usinghighly sensitive mass spectrometric methods; analysis of cellularlocalisation and metabolism of brain glycosphingolipids in orderto clarify their functions especially during critical stages ofdevelopment, aging and disease (neurodegeneration, tumours)

Glycosphingolipids (gangliosides) and cholesterol are constitu-ents of cell membrane lipid rafts – highly organised lipid do-mains involved in signal transduction, cell adhesion and in-tercellular communication. The greatest variety in compositionand specific regional distribution of gangliosides have been ob-served in human brain tissue. In previous studies we establishedthat specific changes of content and composition of braingangliosides may serve as stage specific markers of brain devel-opment, ageing and neurodegeneration. Also, alterations inganglioside catabolism have been noticed both in brain and pe-ripheral tissues in Alzheimer's disease.

(2) cholesterol metabolism in mammalian brain

(3) mutations in the gene for arylsulfatase A (ASA) and changes in kinetic properties and activity of the enzyme – possible as-sociation with neurological disorders

The major physiological substrate of lysosomal ASA is cerebroside-3-sulfate, an importantlipid constituent of oligodendrocyte membranes contributing to maintenance of myelinsheath integrity. Deficiency of ASA causes metachromatic leukodystrophy, a rare diseasecharacterised by progressive demyelination and various neurological symptoms (pyramidaland extrapyramidal signs, progressive spastic quadriparesis). Low ASA activities are found inhealthy individuals and several neurological and psychiatric disorders, due to conditiontermed ASA pseudodeficiency. Although a large number of mutations in the ASA gene havebeen reported so far, only several mutations have been characterised concerning catalyticproperties of the enzyme due to changes in either conformation or concentration of the en-zyme.

Selected papers:

(1) Kra~un I, Kalanj S, Talan-Hranilovi} J et al. Neurochem Int 1992. (2) Kalanj-Bognar S, Rundek T, Fura~ et al. J Gerontol A Biol Sci Med Sci2002. (3) Vukeli} @, Kalanj-Bognar S. Glycoconjugate J 2001. (4) Bognar SK, Fura~ I, Kubat M et al. Arch Med Res 2002. (5) Fon Tacer K,Kalanj Bognar S, Waterman M R, Rozman D. J Ster Biochem Mol Biol 2003. (6) @untar I, Kalanj-Bognar S et al. Clin Chem and Lab Med 2004.

Ganglioside pattern of the adult human cerebellar tissue(left) and gliosarcoma (right) as revealed by thin-layerchromatography and laser densitometry.

Dependence of the initial reactionvelocities on the substrate concentration(36.5 °C, pH=5.0; the best fit of the datausing the Michaelis-Menten equation). Incollaboration with Bla`enka Foreti}, PhD(Dpt. Chemistry&Biochemistry).

Cholesterol metabolism in mammalian brain has not yet been fully clarified. Myelination and dynamic rebuilding andremodelling of the neuronal membranes (particularly during brain development) require precise control and regulation ofcholesterol homeostasis in brain. We are interested in regional and age-dependent expression of cholesterogenic genes inthe brain; intercellular transport of cholesterol (neurons-glia communication); structural interactions of cholesterol withglycosphingolipids in membrane lipid domains; changes in physical and chemical properties of the membranes leading toredistribution of membrane constituents and alterations of cellular functions.

Mutations associated withASA pseudodeficiencydetected in patients withcerebral palsy

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratory of Medical Genetics,Clinical Neurogeneticsand Muscular DisordersHead: Professor Nina Canki-Klain, M.D.Ph.D.

nina.canki-klainºzg.htnet.hrPediatrician-geneticist

Staff: Astrid MILI], M.Sc., Martina MALNAR, Jasna LALI], Marija VIDAKOVI]

The goal of the laboratory is to conduct basic research into the origins and molecular spectrum of monogenic muscular andneurological disorders with emphasis on epidemiology situation in Croatia in order to find improved therapeutic measures,to prevent, ameliorate or cure these disorders. Differential diagnosis of these disorders requires the careful application of abroad range of disciplines: clinical assessment, immunoblotting using a panel of antibodies and extensive molecular geneticanalyses.We started by a wide range approach to the analysis of affected muscles. Selection of patients is done at Division ofNeurogenetics (Head Nina Canki-Klain), Dept of Neurology, Zagreb University Clinical Centre.Muscular dystrophy (MD) includes a spectrum of disorders caused by loss of the linkage between the extracellular matrix andthe actin cytoskeleton. Within this are the forms of limb-girdle muscular dystrophy (LGMD) caused by distinct patho-physiological mechanisms. For example, the prevalent autosomal recessive LGMD in our population is calpainopathy causedby loss of calpain-3, that may exert its pathological influence either by perturbation of the IkappaBalpha/NF-kappaB path-way, or through calpain-dependent cytoskeletal remodelling. Deficiency of dysferlin (LGMD2B) disrupts sarcolemmal mem-brane repair,and seem to be frequent, insidious, clinically very heterogenous disorder.

CALPAINOPATHY or LIMB GIRDLE MUSCULAR DYSTROPHY TYPE 2A(LGMD2A)

A. CAPN3 GENE ANALYSIS: (Table 1); B. HAPLOTYPE ANALYSIS in order to determine the origin and hopefully age of themost prevalent 550delA mutation; C. PROTEIN ANALYSIS (Fig.1); D. STUDY OF CALPAIN 3 FUNCTION: Analysis of calpain3-titin interactions in order to identify signalling pathways originating from titin and those regulated by calpain 3. This wouldexplain calpain 3 function in the cell and mechanism of LGMD 2A

DYSFERLINOPATHY or LIMB GIRDLEMUSCULAR DYSTROPHY TYPE 2B (LGMD2B)

A. INDIRECT GENE ANALYSIS: linkage analysis with 4 polymorphic markers (Fig. 2.)B. PROTEIN ANALYSIS: Non-invasive diagnostics of dysferlin from peripheral blood: 1. Isolation of monocytes using Ficolland Percoll followed by SDS-PAGE and immunoblot analysis of dysferlin and isolation of monocytes using CD 14 microbeads,the most reliable method for dysferlin analysis is now in process.

Selected publications:Canki-Klain N et al. Am J Med Genet 2004; 125A: 152-156.Canki-Klain N et al. Croat Med J 2000; 41: 389-395.Canki-Klain N. Eur J Obstet Gynecol Reprod Biol 1994; 55(1): 17.Canki N et al. Zdrav Vestn 1983; 52: 567-70.Canki N et al. Ann Génét 1979; 22: 33-9.

Fig.1 Western blot analysisof calpain 3 from muscle:a)normal; b) affected

MUTATIONS FREQUENCY

550delA 74.1%

R541W 8.6%

P82L 5.2%

delFWSAL 3.5%

Y537X 1.7%

R49H 1.7%

Unidentified 5.2%

TOTAL 100%

Table 1. Study of 29 unrelated LGMD 2A Croatianfamilies revealed presence of 6 mutations,accounting for 95% of CAPN3 chromosomes

Fig. 2.

On going projects:MZOS, No.0108052COGITO 2005/6 ( collaborating institution INSERM U567).ECO-NET 2004/5 (collaborating institution : Généthon / CNRSUMR8115).

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratoryfor NeuropathophysiologyHead: Marijan Klarica, MD, PhD, associate professor

e-mail: mklaricaºhiim.hrMembers: Inga Mandac, MD, assistant

e-mail: imandacºyahoo.comGoran Ivki}, MD, senior assistante-mail: givkicºhiim.hr

The investigation of physiology and pathophysiology of the cerebrospinal fluid (CSF) and intracranial pressure takes place inthe laboratory. At the present the following projects are under way:

1. Fate of cerebral metabolite and drugs in the CSF system

- it is found that the cerebral capillaries act as the main avenue for elimination of brain metabolite and anionic drugs by activetransport- the CSF is a closed system which communicates with blood only via cerebral capillaries but not by way of circulation and ab-sorption of CSF into dural venous sinuses as postulated by the classic hypothesis of CSF secretion, circulation and absorption

2. Pathophysiology of hydrocephalus

- in a new model of acute occlusion of aqueduct of Sylvius incats, the size of isolated brain ventricles and CSF pressurechanges in isolated ventricles and subarachnoid space are in-vestigated to elucidate the pathophysiology of acute hydro-cephalus- the results indicate that for dilatation of isolated ventriclethe mechanical obstruction by itself is not enough

3. The mechanism of intracranial pressure regulation

- it is for the first time that simultaneous pressure changes inbrain ventricles, cervical and spinal epidural space, spinaland cranial subarachnoid space are registered during bodyposition changes, the CSF infusion and cerebral cold injuryto elucidate why the CSF pressure changes are different incranial than in spinal cavity

4. The mechanism of action of osmotic drugs on intracranial hypertension

- our results indicate that intravenous application of hyperosmolar solution of osmotic drugs causes fall of the CSF pressure inintact craniospinal cavity by reduction of spinal CSF volume but not by dehidration of brain tissue, reduction of intracranialCSF volume or decrease of CSF secretion as generally assumed.

Selected publications:Ore{kovi} D, Klarica M, Vuki} M. Medical Hypotheses 2001Zmajevi} M, Klarica M, Varda R, Kudeli} N, Bulat M. Neurosci Let 2002Ore{kovi} D, Klarica M, Vuki} M. Neurosci Let 2002

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratory of NeurooncologyHead: Assistant professor Nives Pe}ina-[laus, Ph.D.

ninaºmef.hrStaff: Tamara Niku{eva Marti}, B.Sc. tmarticºmef.hr

Martina @igmund, M.D; Milka Kljai}, M.D.Vili Bero{, M.D.Kre{imir Radi}, Jelena Peri}

Our laboratory studies the molecular basis of human brain tumors. The research focuses on genetic abnormalities in brain tu-mors with emphasis on genes that are key components of the wnt signalling pathway. The wnt pathway is often modified inhuman tumors and is also critical in brain developmental processes. It is named after the wnt secreted signalling proteins inmouse and man. Our particular interest lies in studying changes in APC, beta-catenin and E-cadherih genes in order to under-stand molecular and genetic mechanisms that govern the formation and progression of different types of brain tumors. In amajor project we focus our energy on understanding and defining the pathway of tumor formation that is critically impor-tant because it gives researchers an improved ability to detect changes in genes and predict whether a patient is likely to re-spond to treatment.The Laboratory of Neurooncology is also involved in the formation of the bank of brain tumor tissues. We collected andstored an extensive Brain tumor bank resource and encourage young scientists and students to research in neurooncolgy. Weare also very much in the fulfillment of an educational dimension of the research carried out in our laboratory.We are collaborating with the Department of Neurology, University Hospital Sisters of Charity, Zagreb and Clinical Institute ofLaboratory Diagnosis, Clinical Hospital Centre Zagreb. The range of molecular techniques in our laboratory includeimmunohistochemistry, Western blotting, DNA extraction from tissue and blood, PCR reaction, Loss of heterozygosity analy-sis, RFLP, SSCP and PAGE.

Selected publications:Paveli} K, Pe}ina-[laus N, Spaventi R. Int. J Develop Biol 35: 209-214, 1991.[torga D., Pe}ina-[laus N, Paveli} J, Paveli}, ZP, Paveli} K. Int J Exp Path 73: 527-533, 1992.Gall-Tro{elj K, Ku{i} B, Pe}ina-[laus N, Paveli} K, Paveli} J. Eur J Clin Chem Clin Biochem 33: 733-737, 1995.Pe}ina-[laus N, Paveli} K, Paveli} J. J Mol Med 77: 446-453, 1999.Pe}ina-[laus N, [laus M. Homo 51: 151-155, 2000.Pe}ina-[laus N, Gall-Tro{elj K, Kapitanovi} S, Paveli} J, Paveli} K. Coll Antropol 26: 85-88, 2002.Pe}ina-[laus N. Cancer Cell International 3 :17, 2003.Pe}ina-[laus N, Gall-Tro{elj K, [laus M, Radi} K, Niku{eva-Marti} T, Paveli} K. Pathology 36: 145-151, 2004.Pe}ina-[laus N, Niku{eva-Marti} T, Gall-Tro{elj K, Radi} K, Hra{}an R. In vivo 19: xxx-xxx, 2005.

On going project:MZOS, No. 0108215

Fig.1 Lane 2 - lossof heterozygosityat APC gene (exon11/Rsa I/ RFLP) in anoligoastrocytoma

Fig.2 Lane 2 - lossof heterozygosityat E-cadheringene in ameningeoma

Fig.3 Wnt signaling pathway demonstrating its keycomponents

Fig.4 15% polyacrylamide gel showing D16 S752 markerlinked to the E-cadherin gene: Lane 1 –RER-positive

pheochromocytoma sample; lane 2-heterozygouscorresponding normal tissue sample; lane 3- marker

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Cytogenetic LaboratoryLukrecija Bre~evi}, Ph.D., Ass.Prof.lbr25ºhotmail.com

RESEARCH AREA:

Molecular cytogeneticsComparative genomic hybridization (CGH)Multicolour FISH

My research interests have focused on applications of molecular cytogenetics particularly in relation to human disease, inorder to identify and elucidate the nature of chromosomal abnormalities (cryptic and submicroscopic balanced and unbal-anced rearrangements) in patients with neuro-developmental delay/and or congenital malformations and cancer.

Selected Publications:1. Brecevic L, Verdorfer I, Saul W, Trautmann U, Gebhart E. Anticancer Res. 2001 Jan-Feb;21(1A):89-92.2. Brecevic L, Basaran S, Dutly F, Rothlisberger B, Schinzel. A. J Med Genet. 2000 Dec;37(12):964-7.3. Röthlisberger B, Kotzot D, Brecevic L, Koehler M, Balmer D, Binkert F, Schinzel A. Eur J Hum Genet 1999 Dec 7:8 873-83.4. Schinzel A, Kotzot D, Brecevic L, Robinson WP, Dutly F, Dauwerse H, et al.. Eur J Hum Genet 1997 Sep-Oct 5:5 308-145. Schrimpf SP, Bleiker AJ, Brecevic L, Kozlov SV, Berger P, Osterwalder T, et al. Genomics 1997 Feb 15 40:1 55-62.6. Schinzel A, Brecevic L, Bernisconi F, Binkert F, BerthetF, Wuollud A, Robinson WP. J Med Genet 1994;31:798-803.

Fig.2. Multicolor FISH. The identification of smallsupernumerary marker chromosomes (sSMC) bymulticolor centromere-specific FISH (Fig.2a). Thecharacterization of sSMC as r(3)(::p12->q13.2::)found in prenatal diagnosis, and analysis ofderivative chromosomes 8 with extra material ofunknown origin in AML by multicolor banding(MCB), are presented on Fig.2b and Fig.2c,respectively.

Fig.2. Comparative genomic hybridization, CGH. By hybridizingDNA from the patient/tumor labeled with a green fluorochrometogether with normal DNA labeled in red onto normalmetaphases, analysis of the ratio of red to green along thechromosome identifies regions amplified or deleted in thepatient sample. Hr-CGH offers the opportunity to determine theprevalence of cryptic and sub-microscopic rearrangements atthe whole genome level. Fig.2a presents a CGH metaphase ofan AML sample. The profiles of chromosomes 20 of the sameAML sample are shown on Fig.2b-c

Fig.1. The detection of specific microdeletions and microduplicationsbeyond the resolution of routine cytogenetics. A new 1p36microdeletion syndrome detected by subtelomere FISH DNA specificprobe (Fig.1a), and the same abnormality detected by comparativegenomic hybridization (Fig.1b).

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Molecular Basis of the Inhibi-tion of IL-6 mRNA Expressionby BMP-6Principal Investigator: Ljiljana Poljak MD, PhDE-mail: poljakmefºyahoo.com

Project Description

Many biological processes are controlled at the level of transcriptional regulation. Minimally two functions are required fortranscriptional control: the ability to bind specific DNA sequence and the ability to transactivate by recruiting and modulatingthe basal transcriptional machinery.Transcriptional activation of IL-6 gene is highly dependent on NF-?B activity but also on its cross talk with other signling path-ways like Smad signaling. An example of a such synergisam represents the formation of Smad-1/STAT-3 complexes bridgedby general transcriptional coactivator p300 on the promotor region of glial fibrilarly acidic protein (GFAP) gene, a marker ofastrocyte differentiation.To get an insight into molecular basis of the observed inhibitory effect of BMP-6 on the IL-6 mRNA expression, we use cell linedeficient in JAK-1 molecule, a mediator of IL-6 signaling pathway upstream to STAT-3. Upon transfection of these cells withplasmids containing Flagged Smad-3, Smad-2 or Smad-1, we follow the expression of IL-6 mRNA as well as its receptors byRT-PCR. In addition, the same kind of experiment is performed on the transgenic cell line overexpresing JAK-1 molecule.Hopefully, by using cell lines genetically modified in a way to make them either deficient or enriched in a specific gene prod-uct considered to be at the crossroad point of different signalization pathway its potential therapeutic value will be deter-mined.

Selected Publications:Fransozo G, Carlson L, Poljak L, Shores E.W, Epstein S, Leonardi A, Grinberg A,Tran A, Scharton-Kersten T, Anver M, Love P, Brown K. andSiebenlist U. (1998) Mice Deficient in Nuclear Factor (NF)-kB/p52 Present with Defects in Humoral Responses, Germinal Center Reactions andSplenic Microarchitecture. J Exp Med 187:147Poljak L, Carlson L, Cunningham K, Kosco-Vilbois M. and Siebenlist U. (1999) Distinct Activities of p52/NF-?B Required for Proper SecondaryLymphoid Organ Microarchitecture: Functions enhanced by Bcl-3. J Immunol 163:6581Mari} I, Poljak L, Zori~i} S, Bobinac D, Bosukonda D, Sampath K.T. and Vuki~evi} S. (2003) Bone morphogenetic protein-7 Reduces theSeverity of Colon Tissue Damage and Accerelates the Healing of Inflammatory Bowel Disease in Rats. J Cell Physiol 196:258

Nature Reviews Immunology 3: 900-911 (2003)

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Croatian Institute for Brain ResearchURL: http://www.hiim.hr

Laboratoryfor Electron MicroscopyHead: Prof. Ljiljana Kostovi}-Kne`evi}

M.D., Ph.D. liliºmef.hr

Laboratory for Neurogeneticsand Developmental GeneticsURL: http://neurogenetika.hiim.hr

Head: Assist. Prof. Sre}ko Gajovi}, M.D., Ph.D.srecko.gajovicºhiim.hr

Staff: Dinko Mitre~i}, M.D. dominicºmef.hrMarija ]urlin, M.Sc. milcicºmef.hrSandraMavri} sandramavricºyahoo.comIris Elezovi}

The general scope of our laboratory is to investigate gene function in developing and adult central nervous system. In orderto assign a function for a gene in mammals, one of the approaches is generation of genetically modified mice with modifica-tions of genes of interest. Analysis of phenotype changes of the mutated mice show the consequences of the genetic change,and give an insight in gene function in a context of complex multicellular organism.

The mutant mice we analyze were produced by gene trap. In gene trap method anonhomologous DNA vector, containing a splice acceptor and fused promoterless

genes lacZ and neoR, is used to genetically modify embryonic stem cells. Afterselection and screening the corresponding mouse lines were produced.

The nature of the inserted vector enables expression pattern analysisas endogenous promoter of the affected gene controls lacZ gene.

The insertion of the gene trap vector disturbed the tagged gene,hence the phenotype changes of the homozygous mice can be

determined, which should reveal gene function.Gene trap line with modified Stam2 gene is currently in focusof our interest. Stam2 (signal transducing adapter molecule 2)is expressed during development in the neural tube and in theheart, and in the adult in brain cortex and hippocampus (Fig.1). Its presumed function is in the endosome-mediated cellsignaling, and endo- and exocytosis.Another line of the research in the laboratory is concernedwith development of the neural tube in the caudal part ofthe embryo (tail bud) via secondary neurulation. In order to

understand morphogenetic mechanisms in the caudal partof the embryo and connect it with development of spinabifida, two spontaneous mouse mutations are analyzed:splotch, which is a mouse model for spina bifida, and trun-cate, with defects in caudal notochord (fig. 2).

Selected publications:Mitre~i} D et al. (2004) Cells Tissues Organs 178, 23-32Belovari T et al. (2004) Anat Histol Embryol 33, 90-95Burdon KP et al. (2003) Am J Hum Genet 73, 1120-1130Muro AF et al. (2003) J Cell Biol 162, 149-160Muro AF et al. (2000) Blood 95, 3978-3985

Ongoing projects:MZOS: No. 0108117No. 0108402

Figure 1. Expression pattern of Stam2 gene in cortex andhippocampus as revealed by histochemical staining forbeta-galactosidase (blue color) of horizontal vibratomesection of adult mouse brain.

Figure 2. Caudal part of the splotch homozygous embryoshowing spina bifida (SB) and curled tail (T). LB – limb bud.11.5-day embryo viewed under stereomicroscope.

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Center for Clinical Researchin NeuroscienceSchool of Medicine University of ZagrebSalata 12, 10 000 Zagreb, Croatia

Director: Marijan Klarica, MD, PhDSecretary: Ravena ^izmi}

The organisation of a Center for ap-plication of scientific discoveries is acomplex problem. In the recent yearssuch Centers have been organized indeveloped countries to coordinate thecollaboration of several teams fromvarious scientific institutions and indus-try.

Our Center for Clinical Research inNeuroscience was founded in 1998 bySchool of Medicine University ofZagreb. The most important aim of theCenter is to coordinate the program oflong lasting investigations in neurol-ogy, neuroradiology, neurosurgery,psychiatry and allied fields in collabora-tion with the Croatian Institute forBrain Research (CIBR) and Clinics ofSchool of Medicine as well as coordina-tion of our efforts with other institu-tions of high learning in the field of re-search and teaching. The Center isnon-profit organization with effica-cious and low cost administration (gov-erning committee, director and secre-tary) with the following units: unit foreducation, unit for application of re-search in neuroscience, unit for infor-mation and publications, and unit forimaging of the central nervous system.Diagnostic Center «Neuron» have beenestablished in year 1999, mainly for thefacilitation of long lasting research inneurology, psychiatry, neurosurgery,pathology, cytogenetics and laboratorydiagnostics.

Our Center participated in organisa-tion of several symposia and neurosci-ence schools together with CIBR andDiagnostic Center “Neuron”. Also,technological project «The neuro-surgical endoscopic contact ultrasonicprobe» was developed under sponsor-ship of our Center. Department forNeurosurgery School of Medicine, Fac-ulty of Electrical Engineering and Com-puting, Brodarski Institute and our Cen-ter have been working together on de-velopment of this project. The result is aprototype of the new surgical «knife»NECUP 2 which is under scientific andclinical evaluation at the moment. In

the future perspective Center has a twoadditional technological projects withbefore mentioned collaborators.

It seems that collaborations of basicscientists, clinicians and other experts

can be efficacious even in our low bud-get situation since the Center succeedsto connect basic and clinical investiga-tions in specific projects at low runningand administrative cost.

The neurosurgical endoscopic contact ultrasonic probe

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Diagnostic Center Neuron

In the Pursue of ExcellenceA major strength of the CIBR is the capacity to study brain using the combined perspectivesof basic and clinical research.In order to gather together various clinical neuroscience groups, Diagnostic Center Neuronwas established in 1999 and is affiliated with the CIBR and its Center for Clinical Researchin Neuroscience.

Infrastructure

Diagnostic Center Neuron comprises of:

– Magnetic Resonance Unit

– Psychiatric Unit

– Neurology and Neuropediatrics Unit

– Neuropathology Unit

– Cytogenetics Unit

– Department for Clinical Trials.

In diagnostics we use state-of-the-art diagnostic equip-ment including 2T magnetic resonance device with spectroscopy; 128 multi-channel EEGwith whole brain mapping and sleep analysis; Evoked potentials (inconstitution); electron,confocal, and epi-fluorescence motorized research microscopy as well as modern informa-tion technology infrastructure. Thus the diagnostic centerprovides excellent diagnostic and out-patient services

Clinicians and researchers

Members of neuroscience groups affiliated with DiagnosticCenter Neuron include prominent Croatian clinicians andhealth care professionals:Prof.dr.sc. Vera Folnegovi}-[malcProf.dr.sc. Bo`o Kru{linProf.dr.sc. Vlasta Meja{ki-Bo{njakProf.dr.sc. Marta Ljube{i}Doc.dr.sc. Lukrecija Bre~evi}Doc.dr.sc. Neven HenigsbergDr.sc. Marko Rado{Mr.sc. Elizabeta Radoni}Dr. med. Goran Ivki}Dr.med. Helena [aracMr.sc. Tomislav GojmeracIng. Igor Fu~kanIng. Damir Turkalj

Teaching and research

The Diagnostic Center Neuron participates in CIBR compre-hensive teaching programs for graduate and postgraduatestudents, postdoctoral fellows, and residents. Research fo-cuses on 3D MR imaging and volumetric analysis; normaland pathological neurodevelopment, and genetic factors inthe treatment of psychotic disorders. The scope of clinicalresearch is widening to clinical trials and early phases ofdrug development. Department for Clinical Trials becamethrough CIBR in 2004 the full member of EuropeanComission funded (FP6) scientific project “Genomic-basedtherapies for depression”.

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University of ZagrebPh.D. Program in Neuroscience

Introductory Note: At the School ofMedicine, University of Zagreb, there isalready approved PhD Program entitled«Biomedicine & Health Sciences»; thepart of that PhD program is a special-ized «Neuroscience Program» (Coordi-nator: Professor Ivica Kostovi}, MD,PhD). Selected courses from that Neu-roscience Program (marked with aster-isks in the following text) were used asthe basis for preparing this proposal ofthe University PhD Program in Neuro-science; in addition, some of these al-ready reviewed and approved courseswere slightly modified in order to avoidunnecessary overlaps with newly pro-posed courses. On the other hand, thenewly proposed courses were selectedand proposed on the basis of the fol-lowing criteria:

1. For the majority of new courses,course leaders are distinguishedand internationally recognized re-searchers who are members of TheInternational Scientific AdvisoryBoard of the Croatian Institute forBrain Research (Professors Kre{imirKrnjevi}, Mirko Dik{i} and Ante L.Padjen from the McGill University,Montreal, Canada; Professor Ye-hezkel Ben-Ari, the director of In-stitut de neurobiologie de la médi-terranée, INSERM, Marseille, Fran-ce; Professor Harry B.M. Uylings,head of Cognition and Neuroima-ging at The Netherlands Institutefor Brain Research in Amsterdam;Professor Ronald L. Schnaar, theChairman of Departments of Phar-macology and Neuroscience at TheJohns Hopkins University School ofMedicine in Baltimore, U.S.A.; Pro-fessor Mirjana Randi} from the De-partment of Biomedical Sciencesof the Iowa State University, Ames,U.S.A.; Professor Roland Pochet,the Director of ULB Laboratoired'Histopatologie in Bruxelles, Bel-gium; Professor Tamas F. Freund,Director of the Institute of Experi-mental Medicine, Hungarian Acad-emy of Sciences, Budapest andcurrently the President of theFENS; Assistant Professor Nenad[estan, Department of Neurobio-logy, Yale University School of Me-dicine, New Haven, U.S.A.).

2. For other new courses, courseleaders are internationally recog-nized researchers who have re-

cently established collaborative re-search projects with our young in-vestigators – usually, but not ex-clusively, with young investigatorswho were formerly trained in theirlaboratories (Professor ThomasDeller from Germany; Dr. Moni-que Esclapez from Marseille, Fran-ce; Professor Michail S. Davidofffrom Hamburg; Professor Sigis-mund Huck, Deputy Director ofthe Brain Research Institute in Vi-enna, Austria); Professor Jean-Pi-erre Julien, the director of researchon neurodegeneration in Canada(University Laval, Canada); Profes-sor Peter McGuffin, director of theSocial, Genetic and Developmen-tal Psychiatry Centre, MRC, Lon-don, UK; Dr. Nenad Bogdanovi}from Karolinska Institute in Swe-den; Professor Damir Janigro, di-rector of the Cerebrovascular Re-search at The Cleveland ClinicFoundation, Ohio, USA; ProfessorDaniela Prayer from the Depart-ment of Neuroradiology, Univer-sity Clinics for Radiodiagnostics,University Vienna, Austria); Profes-sor Majda M. Thurnher from theDepartment of Radiology, Univer-sity Vienna, Austria; ProfessorMijna Hadders-Algra from the De-velopmental Neurology, Univer-sity Hospital in Groningen, TheNetherlands.

3. For new courses proposed by Cro-atian researchers, course leadersare as a rule active researcherswith established international col-laboration, currently serving asheads of Sections and Labora-tories at the Department of Neu-roscience of the Croatian Institutefor Brain Research.

THE FIRSTCREDIT GROUP(CORE COURSES, METHODOLOGI-CAL COURSES AND GUIDED TUTO-RIALS)

CORE COURSES (already ap-proved courses are marked withasterisk):

Introduction to research in neurosci-ence (laboratory rotations)

*Lackovi} Zdravko: Neurotransmitters

Petanjek Zdravko & Esclapez Moni-que: Introduction to Neurobiology

Dik{i} Mirko: Introduction to Neuro-chemistry

Kostovi} Ivica & Juda{ Milo{: HumanNeuroanatomy

*Kostovi} Ivica: HumanDevelopmental Neurobiology

[estan Nenad: Molecular Neurobio-logy of the Developing Cerebral Cortex

Kru{lin Bo`o: Introduction toDevelopmental Neuropathology

*Juda{ Milo{: Human EvolutionaryNeurobiology

Tadinac-Babi} Meri & Juda{ Milo{:Introduction to EvolutionaryPsychology

Tadi} Zoran: Introduction to AnimalBehaviour

Juda{ Milo{: History of NeurosciencePrayer Daniela & Rado{ Marko:

Structural and FunctionalNeuroimaging

METHODOLOGICAL COURSES& GUIDED TUTORIALS (all alreadyevaluated & approved):

Kostovi}-Kne`evi} Ljiljana & Gajovi}Sre}ko: Morphological Research Me-thods and Electron Microscopy in Neu-roscience

Kostovi}-Kne`evi} Ljiljana: ElectronMicroscopy of the Developing HumanBrain

Petanjek Zdravko.: Demonstration ofNeuron Structure by ConfocalMicroscopy and DigitalMicrophotography

Petanjek Zdravko & [imi} Goran: Me-thods of Neuron Reconstruction andStereology

Petanjek Zdravko: PreciseIdentification of Cortical Areas in AdultHuman Brain In Vivo

Petanjek Zdravko & [imi} Goran:Histochemistry and Immunochemistryof Neurons and Neuronal Pathways inthe Developing Human Brain

Petanjek Zdravko & [imi} Goran:Non-radioactive In situ Hybridizationon Human Brain Tissue

Jernej Branimir: Methods of RNAIsolation From Brain Tissue

Jernej Branimir: Methods of DNAIsolation From Leukocytes

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Jernej Branimir: The Amplification ofGenomic DNA by Polymerase ChainReaction (PCR)

Jernej Branimir: The Analysis ofHuman Gene Polymorphisms

Jernej Branimir: The Analysis of GeneExpression in Neurons

Jernej Branimir: Detection andIdentification of Proteins by WesternBlotting

Jernej Branimir: The Determination ofNeurotransmitters and TheirMetabolites in the Brain Tissue (HPLCand SPF Methods)

Jernej Branimir: The Kinetics of theSynaptic Transmembrane (Serotonine)Transporter

Jernej Branimir: The Kinetics of theSynaptic Enzyme (MAO-B)

Jernej Branimir: The Kinetics of the(5-HT-2A) Receptor Binding

Juda{ Milo{ & Rado{ Marko: In vivoQuantitative MRI Analysis of Adult andDeveloping Human Brain

Ljube{i} Marta: The Evaluation ofCognitive Functioning, Communicationand Language in Children

SECOND CREDIT GROUP(FIELD RELATED COURSES, CLINI-CAL COURSES, AND COURSESFROM OTHER UNIVERSITY Ph.D.PROGRAMS)

FIELD RELATED & CLINICALCOURSES (Already approvedcourses are markedwith asterisk):

Cellular & Molecular Neurobiology:

Sopta Mary: TranscriptionalRegulation in the Brain

*Gajovi} Sre}ko: Gene Targeting inMammals

Krnjevi} Kre{imir: MolecularMechanisms of Synaptic Signalization

*Banfi} Hrvoje: Cell SignalingPochet Roland: Calcium Signalization

in the Nervous System*Heffer-Lauc Marija & Schnaar

Ronald L.: Molecular Biology of MyelinKalanj-Bognar Svjetlana: Lipid Rafts:

Structural-functional Units ofMembranes in the Central NervousSystem

*[alkovi}-Petri{i} Melita: MolecularEndocrinopharmacology

Davidoff Michail S.: Characteristics ofthe Diffuse Neuroendocrine System

Cellular & Systems Neurophysiology:

Randi} Mirjana: Cellular Neurophy-siology

Huck Sigismund: Introduction toPatch-clamping

Padjen Ante L.: Neurophysiology ofCentral Neuronal Circuits

Deller Thomas: Cellular andMolecular Basis of Axonal Sprouting inthe Hippocampus Following Lesion

Ben-Ari Yehezkel: Experimental Mo-dels of Epilepsy and the Role of GABA inCortical Development

Janigro Damir: The Physiology ofCerebral Circulation

*Klarica Marijan: Pathophysiology ofthe Brain and Cerebrospinal Fluid

Developmental Neuroscience& Pediatric Neurology:

*Gajovi} Sre}ko: How to Become aNeuron?

*Bre~evi} Lukrecija: Genetics ofMental Retardation and BrainMalformations

*Latin Vi{nja: Detection of Fetal Hy-poxia

*[krablin Snje`ana: Perinatal Periodin Neurologically Disabled Newborns

*Meja{ki-Bo{njak Vlatka & Had-ders-Algra Mijna: Developmental(Pediatric) Neurology

*Bari{i} Nina: Pediatric EpileptologyBari} Ivo: Inherited Metabolic

Diseases Affecting Central NervousSystem

Psychiatry, Behavioral Neuroscience& Neuroimaging:

*Rado{ Marko: Advanced ClinicalNeuroimaging

Thurnher Majda: MR Imaging of theSpinal Cord

*Folnegovi}-[malc Vera: Etiologyand Classification of Psychoses

*Jakovljevi} Miro: Clinical Psycho-pharmacology

Henigsberg Neven: Neurobiology ofthe Treatment of Psychiatric Disorders

McGuffin Peter & Henigsberg Neven:Psychiatric Pharmacogenomics

*Jernej Branimir: SerotonergicCorrelates of Behavioral Disorders

*Jernej Branimir: MolecularPhysiology of Synaptic Function:Serotonergic Synapse as a Model

*[imi} Goran: Neurobiology of AgeingUylings Harry B.M.: Cognitive

Flexibility and Orbital Prefrontal Cortex

Neurology, Neuropathology& Neurosurgery:

Bogdanovi} Nenad: Brain Banking &European Brain Bank Network

*Relja Maja: Movement Disorders*Relja Maja: Clinical Neuropharma-

cology*Vida Demarin: Neurosonology*Canki-Klain Nina: Genetic Basis and

New Diagnostic Approaches to Mono-genic Neuromuscular Disease

Julien Jean-Pierre: Molecular Neuro-pathology

*@arkovi} Neven: Experimental Neu-ropathology: Oxidative Stress of theCentral Nervous System

Osmak Maja: The Outcome of Neu-ronal Damage: Repair or Death

Pe}ina-[laus Nives: MolecularGenetics and Neurooncology

Mikli} Pavle & Paladino Josip: Neuro-transplantation and RestorativeNeurosurgery

COURSES FROM RELATED UNIVER-SITY Ph.D. PROGRAMS:(N.B.: all listed courses are al-ready evaluated as a part of pro-gram «Language Communicationand Cognitive Neuroscience»)

Jernej Branimir: Synaptic transmissionand its disorders

Klarica Marijan: Drugs and brainKova~evi} Melita: Language

acquisition and developmentLon~ari} Sven: Analysis and

understanding of imagesLjube{i} Marta: Early communicationSupek Selma: Magnetoencephalo-

graphyZarevski Predrag: Memory, meta-

cognition and intelligence

Ivica Kostovi}

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Scientific Education at theDepartment of ClinicalNeuroanatomy, University of Frankfurt(MSc. Mario Vuk{i}, MD)

I have spent last two years (January2003 – January 2005) at the Depar-tment of Clinical Neuroanatomy (Ana-tomy I), Medical School, University ofFrankfurt as a postdoctoral fellow ofthe Graduate Program “Neural Pla-sticity: Molecules, Structures, Fun-ctions” at that university. Clinical Neu-roanatomy is one of the three depar-tments of the Institute of Anatomy inFrankfurt, also called the SenckenbergAnatomy.

The name of the physician anddonator Johanna Christiana Sencken-berg is well known in all Frankfurt area.He was born in 1707 as son of JohannHartmann Senckenberg, “physikus pri-marius” of the then independent Cityand State of Frankfurt. After earninghis doctoral degree, he practiced me-dicine in the footsteps of his father'sprofitable career and became “phy-sikus ordinarius” in Frankfurt.

His private life was less successful;after the death of his third wifeSenckenberg decided to live his life as awidower and to donate his money tovarious public welfare projects. Usinghis private funds, he established the“Dr. Senckenbergische Stiftung” (Dr.Senckenberg Foundation), which aimwas (and still is) to improve publicmedical care and medical education ofphysicians. In 1766, the foundation setup a medical and chemical institute, alibrary, a greenhouse, a public hospitaland a “theatrum anatomicum”, whichevolved into the present “Dr. Sencken-bergische Anatomie”. Hence, the “Dr.Senckenbergische Anatomie” is olderthan the University of Frankfurt itselfthat was founded only in 1914; actuallythe Institute of Anatomy was one of thefounders of this university.

Unlike his successful and long-termpublic projects, Johann Christian Sen-ckenberg continued to have bad luck inhis private affairs. In 1772, whilechecking the construction site of thepublic hospital, he climbed onto a highscaffold, fell off, and died. Only twodays later, Johann Christian Sencken-berg's cadaver was the first corpse tobe dissected in the anatomical theatreof his very own foundation.

When speaking about Anatomy inFrankfurt, we certainly need to mentiona married couple of scientists, Bertaand Ernst Scharrer, to who we owe thediscovery of secretory, hormone pro-ducing nerve cells. They also developeda far-reaching concept regarding thebiological role of neurosecretion. TheScharrers' concept of neurosecretion,together with Wolfgang Bargmann'sdiscovery of the hypothalamo-neuro-hyophyseal neurosecretory pathway,has led to the rise of an entirely newbiomedical discipline, i.e. neuroendo-crinology.

In mark of respect to the extraor-dinary scientific achievements of Ernstand Berra Scharrer, the Faculty of Me-dicine in Frankfurt decided to name theanatomical lecture hall of the ”Dr.Senckenbergische Anatomi” after thesetwo important researchers – “Ernst undBerta Scharrer Hörsaa”.

The present Dr. Senckenberg Anato-my is a modern institute, divided intothree anatomical departments withemphasis on different fields of re-search. Departments Anatomy II and IIIare particularly interested in the orga-nization of the photoneuroendocrineand circadian systems of diverse ver-tebrate species, thus continuing Schar-rers tradition of neurosecretion.

The research goal of the Institute forClinical Neuroanatomy (Anatomy I)headed by Prof. Deller is the study ofdegenerative and regenerative proce-sses within the nervous system. Thatmeans, that the Institute studies themolecular and cellular bases of neu-ronal reorganization and convales-cence processes following trauma orinjury to the central nervous system onone hand, and on the other, research isbeing conducted to determine theirroles in neurological disorders, such asAlzheimer’s disease and temporal lobeepilepsy. Prof. Braak, the former headof the department, has developed thestage classification for Alzheimer's di-sease and Parkinson disease (stagesI-VI), which for the first time clarifiedthe true extent of both illnesses, evenat an early stage. Today, the NationalInstitute of Aging (Bethesda, MD, USA)recommends the Braak staging systemas the basis for Alzheimer-related neu-ropathological studies.

The aim of my project in Frankfurtwas to study lesion-induced and ac-tivity-dependent plasticity in the hip-pocampus. For this purpose I used twoin vivo experimental models; entorhinallesion of the perforant pathway andelectrophysiological hyper stimulationof the same fibre system. As the animal

Members of the Department of the Clinical Neuroanatomy in Frankfurt. Dr. Vuk{i} isin the middle of the picture

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model I used transgenic mice whichexpress enhanced green fluorescentprotein (EGFP) in selective subpo-pulation of hippocampal neurons, sothat these neurons are completelylabelled. During my stay in Frankfurt Ihad the opportunity to gain knowledgeof large number of modern neuromor-phological techniques: immunofluo-rescence stanings (double and triplestainings), confocal microscopy and3D-confocal morphological reconstru-ctions of identified neurons. In addition,I also acquired surgical skills forneurosurgical operations of mice andrats, such as stereotaxic operations andlesioning paradigm, as well as neuro-physiological extracellular recoding tec-hniques. Now, I am able to apply all ofthese newly acquired techniques at theCroatian Institute for Brain Research. Aclose collaboration with the Institute forClinical Neuroanatomy in Frankfurt issuccessfully being continued.

And now, several useful tips fortravellers visiting Frankfurt on businessor just briefly passing through in tran-sit. There are many interesting placesyou will come across in Frankfurt, andeveryone can find something for him-self. The river Main separates the city inthe north bank, predominantlybusiness area and therefore nicknamed“Manhattan”, and the south bank withsome of the Germany's finest museumsand historic buildings, narrow alleysand rustic restaurants of Sachsenhau-sen. Pause at one of the noisy tavernsto taste Frankfurt's special brew, applewine. The best places to experienceFrankfurt's specials, frankfurters andapple wine are Wagner and HausWertheym in Sachsenhausen.

Frankfurt is the birth place of theGermany's most celebrated writerGoethe, and today his timber-framedhome is a museum called “Goethe-haus”. The Stadel Art Museum, visually

very attractive museum, features one ofthe most comprehensive art galleries inthe world presenting superior collectionof the works of German 16th centurypainters. You should by no means fail tosee Senckenberg Museum, one of themost significant exploration museumsin Europe, where you can once againexamine some impressive exhibits onthe history of the earth.

The Palmengarten, worth a visit atany time of the year, is world-wideknown for its ample collections of tro-pical plants. For shopping, upmarketGoethestraße is the place where youcan buy German designer clothes muchcheaper than anywhere else. Frank-furters go shopping on the Zeil, one ofthe top-selling streets in Germany.Bringing along credit cards regardlessof which (they take all) is stronglyrecommended.

Mario Vuk{i} MD

"Dementia" – the Courseof Continuing Medical EducationCourse leader: Goran [imi}, M.D., D.Sc.

In step with our growing lifespan,dementia is becoming a widespreadhandicap to the health and well-beingof individuals and a burden on everyhuman society. In the last several years,the increasing prevalence of this tragiccondition has stimulated an explosionof scientific research, which resulted innumerous profound insights and tec-hnical innovations.

From 10th to12th November 2004 inthe Croatian Institute for Brain Researchthe course of continuing medical edu-cation named "Dementia" was held. Thecourse was co-ordinated by Goran [i-mi}. Several leading Croatian authoritiesin the field were participated in thecourse: Vera Folnegovi}-[malc, NinoslavMimica, Marko Rado{, Neven Henigs-berg, Elizabeta Radoni}, Goran Ivki},Mirna Kostovi}-Srzenti} and KristinaGrbi}.

During the course thirteen medicaldoctors who work with dementingpatients were provided with a synthesisof all topics in dementia research,including epidemiology and etiopatho-genesis of dementia, neuroimaging andcerebrospinal fluid analysis of theearliest alterations, biological andgenetic markers for major dementingdisorders (Alzheimer's disease, vasculardementia, frontal and frontotemporaldementia, dementia with Lewy bodies,

hereditary tauopathies, dementia withargyrophilic grains, alcoholic dementia),as well as with the neuropathologicaland neuropsychological aspects ofdementing disorders.

To meet the more and more evidentneed for professional medical handlingof dementia, at the end of the coursethe question of a joint policy forclassification, description and investiga-tion of suspected dementia, demen-tia-like conditions and manifest de-mentia was drawn up. It was concludedthat a Croatian consensus-based docu-

ment should be made as soon aspossible (such as Swedish or Spanishconsensus on dementia diseases) tostimulate the body of physicians toimprove the medical investigation ofpatients with dementia and demen-tia-like conditions, thereby increasingthe possibilities of providing adequatetreatment and care. The course will beorganized again in November this year.For more information, please go tohttp://dementia.hiim.hr.

Goran [imi}

Course participants with their coordinators

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MEMBER OF THE INSTITUTE SCIENTIFIC ADVISORY BOARD

Leading World Neuroscientists –Pasko Rakic, M.D., Ph.D.Curriculum Vitae

Professor of Neurobiology and Neu-rology, Yale University School of Medi-cine

Degrees: M.D., Ph.D (1960-69) Medi-cine, Developmental Biology and Ge-netics, Univ. Belgrade

M.S. (1978) Honorary, Yale Univer-sity, New Haven, Connecticut

Research Interests: DevelopmentalNeurobiology; Cellular and MolecularMechanisms of Neuronal Proliferation,Migration, Axonal Navigation andSynaptogenesis; Genetic and Epigene-tic Regulation of Neuronal Interactionsduring Development in Spontaneousand Induced Mutations; Neuropatho-logy of Congenital Disorders; Brain Evo-lution.

Professional Experience:

1961-62 Resident in Neurosurgery,University Hospital, Belgrade

1962-66 Clinical and Research Fel-low in Neurosurgery, Har-vard Medical School, Bo-ston

1967-69 Assistant Professor of Dev.Biology & Genetics, Biologi-cal Institute, Belgrade

1969-72 Assistant Professor ofNeuropathology, HarvardMedical School, Boston

1972-78 Associate Professor of Neu-ropathology, Harvard Med-ical School

1978-01 Chairman, Section of Neu-robiology, Yale UniversitySchool of Medicine

1978- Dorys McConnell DubergChair in Neuroscience, YaleUniversity

2001- Chairman, Department ofNeurobiology, Yale Univer-sity School of Medicine

Honors and Awards: Member,National Academy of Sciences, USA,1985; American Academy of Arts andSciences, 1994; Institute of Medicine,1999; Croatian Academy of Arts andSciences, 1990; Serbian Academy ofArts and Sciences, 1985; President, So-ciety for Neuroscience, 1996; President,Cajal Club, 1992; Gerard Prize, SFN,

2002; Bristol-Myers Squibb Neuro-science Award, 2002; Pasarow Foun-dation Award, 2001; Marta PhilipsonAward, Stockholm 2000, Karl SpencerLashley Award, Amer. PhilosophicalSociety, 1986; Francois I Medal, Collegede France, 1986; Pattison Award in Ne-uroscience, 1986; Kreig Award, 1989;F.O. Schmitt Medal and Lecture, 1992;Fyssen International Science Prize,1992; Weinstein-Goldenson ScientificAward (United Cerebral Palsy Foun-dation) 1994; Henry Gray Award, AAA,1996; Grass Foundation Lecture,1985;Ramon y Cajal lecture, Cajal Institute,Madrid; Selby Fellow, Australian Aca-demy of Science, 1983; NINDS JavitsAward, 1984-91, 1991-97; DoctorHonoris Causa, Albert Sent-GeorgyiUniv., Szeged; Doctor Honoris CausaUniversitatis Studiorum Zagrebiensis,1997; Numerous eponymic lecturesincluding the Pickney Harmon (CajalClub), Jenkins Memorial (Oxford), Ber-nard Sacks (AAPN), Yesup (Columbia),Philip Bard (Johns Hopkins), AriensKappers (Royal Netherlands Academyof Sciences), Gordon Holmes (London),Sally Harrington Goldwater, C.N.Wool-sey (Madison), R.J. Terry (St. Louis),

D.O. Hebb (Montreal); Cotzias (Am.Academy of Neurology), Mountcastle(Johns Hopkins); Hunt-Wilson (AANS);James Arthur (Am. Museum of NaturalHistory).

Professional Societies: AmericanAssociation of Advancement of Science(Fellow); American Association of Ana-tomists; American Association ofNeuropathologists; Association of Re-search in Vision and Ophthalmology,Association for Research in Nervousand Mental Disease, Cajal Club; Inter-national Brain Research Organization(IBRO); International Society for Deve-lopmental Neuroscience, InternationalSociety of Psychiatric Genetics, Neuro-science Research Program; Society forNeuroscience.

Editorial Boards: Advances in Neuro-logy (1988-Present); Brain Research(1977- ); Brain Research Bulletin(1973-88); Cerebral Cortex, Co-Editor(1990- ); Developmental Brain Research(1979-2001); Encyclopedia of Neuro-science (1987- ); Exp. Brain Res. (1977-); Glia (1988- ); Human Neurobiology(1982-86); J. Cognitive Science (1988-

Professor Pa{ko Raki} addressing the audience on the occasion of receiving DoctorHonoris Caus at the Zagreb University

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); J. Comp. Neurology (1979-97); J. Ne-urocytology (1975-98); J. Neuroscience(1981-90 and 99-); Neural Plasticity(1991-); Neuroscience (1973- ); Neu-roscience Research (1996-2001).

Advisory Activities: Board Member:Kuratorium, Max-Planck Institute, Ger-many, 1982-96; Councilor, Society forNeuroscience, 1980-84; United NationsCommission on Radiological Protection(ICRP), 1983; U.S. National Committeefor IBRO, 1982-88, Chairman, 1988-92;Advisory Board, British NeurologicalResearch Trust, 1988-93; Board of Tru-stees, Neuroscience Institute, Rocke-feller University (1988-91); AdvisoryBoard, Frontier Research Program, RI-KEN, Tokyo, Japan, 1992-95; ExternalEvaluation Committee, Max-DelbruckCenter for Molecular Medicine, Berlin,Chairman, 1998; Advisory Board,Advisory Board National Alliance forAutism Research, 1994- ; March ofDimes Basil O’Connor Award Com-mittee, 1994-1999; AAAS BiologicalSciences Committee, 1997-2000; Hy-seq Inc., Sunnyvale, 1988-2001 ;Wright Foundation, Geneva, 1996-99;Mutagenesis Center, Jackson Labo-ratory, Bar Harbor, 1999-

NIH Study Sections: Neurology A,1978-82; Visual Sciences B, 1984-88;NIH Special Foreign Currency Grants,1972-78; Special Consultant NIH Pro-gram Project Review Section, 1977;Advisor to NIDA, Grant Review Panel,1975-77; Technical Review Panel onNeuroscience, NIDA-ADAMHA, 1979;NIMH Panel on Neural Development,1993.

Consultant for: National Science Foun-dation; Atomic Energy Control Board(Canada); Canadian Medical ResearchCouncil; The March of Dimes Foun-dation; J.S. Guggenheim MemorialFoundation; Huntington Chorea Foun-dation; Human Frontier Foundation.

Administrative Experience: President,Society for Neuroscience (1996);Chairman, Section 24 (Neurobiology)of the National Academy of Sciences(USA), 1992-95; Chairman, Section ofNeurobiology, Yale University(1978-2001); Founder Department ofNeurobology, Yale University 2001-;Numerous committees at Yale, in-cluding Provostial Committee onNeuroscience; Search Committees forthe Dean and Department Chairs,Dean’s Space Committee, Basic ScienceCurriculum Committee.

Grants: Principal Investigator: P. P. onRegeneration of the CNS, HarvardMedical School (1974-77); Director,Neuropathology of Congenital Disor-ders (HMS); Human Frontier ResearchGrant (1990-93); Director, Javits Centerof Excellence in Neuroscience(1985-90); P.I., Program Project onDevelopmental Neurobiology ofNeocortex (1982-2003); NeurogeneticProcesses in Fetal Brain (1970-present);Prenatal Development of the VisualSystem (1977-present); Stress Acti-vated Protein Kinase in NeuronalApoptosis (1999-present): Notch Sig-naling in the Brain (2001-present).

Organizer of international symposia:Local Circuit Neurons (1975);Development and Modifiability of theNeocortex (1981); Determinants ofNeuronal Connections (1983); Prin-ciples of Neuronal Migration (1984);Brain Beyond Genes (1986); Develo-pmental Determinants of PatternFormation (1987); Dahlem Conferenceon Neurobiology of Neocortex (1987);Functions of Glia (1989); Specificationof Cerebral Cortex (1991); MultipleMolecular Mechanisms for the SameDevelopmental Events (1995); Domainsof Vision (1996); Genetic Factors Con-trolling Forebrain Development, JuanMarsh Foundation, Madrid (2000).

Teaching Experience: Core Neuro-science Course, Harvard (1970-77);Development of the CNS, Harvard(1970-77); Advanced Human Neuro-anatomy, Harvard (1970-77); Neuro-science Course, Stanford (1976); Prin-ciples of Development, CMS, Belgrade

(1971-73). Principles of Neurobiology(Cold Spring Harbor, 1977); Deve-lopment of the Nervous System (ColdSpring Harbor, 1978-86); MolecularNeurobiology of Human Diseases (ColdSpring Harbor, 1988, 1989); Neuro-biology (MBL, Woods Hole, 1978);Immunogenetics (Cold Spring Harbor,1976); Advanced Study InstituteSummer Schools, Crete (Greece, 1978,1997), Varenna (Italy, 1981, 1991),Porto (Portugal, 1982); InternationalSchool of Biophysics, Erice (Italy, 1985),Trieste (Italy, 1986, 1988, 1990, 2001);Review and Update in Neurobiology(MBL, Woods Hole, 1984-94); Deve-lopment of the CNS, Yale (1979-1994);Basic Neurosciences, Yale (1985,1987);Director of the Neuroscience Course,Yale (1978- ); Mentor for Ph.D.students in Neuroscience Program atHarvard and Yale.Profesors Pa{ko Raki} (left) and Ivica

Kostovi} after the ceremony at ZagrebUniversity

The Official Journal of the ZagrebUniversity School of Medicine

Editor-in-Chief

Marko Pe}ina

Editorial Board

Igor Aurer, Darko Bo{njak,Boris Brklja~i}, Vladimir Duga~ki,Marko Duvnjak, Ozren Gamulin,

Sanja Kupe{i}, Branko [imat,Mladenka Vrci}-Keglevi},

Mirzet @i`ak

Production editor

Branko [imat

Secretary

Rosa Zrinskie-mail: rosaºmef.hr

Editorial Office

School of Medicine, Salata 3b,10000 Zagreb, Croatia

Phone: +385 1 45 66 888;e-mail: bsimatºmef.hr

Layout and printing:

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mef.hr reflections

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Personality, Research and TeachingThe generation and transmis-

sion of knowledge are the pri-mary goals of universities. Bothindividuals and institutions differwidely in the fulfillment of thesegoals. Although the factors thataffect these processes are rela-tively poorly understood, severalstudies have produced fairly con-sistent findings with regard tothe personality traits associatedwith successful research andteaching of university professors.

In a meta-analysis of two suchstudies, 452 professors at TheUniversity of Western Ontariowere evaluated on 29 trait di-mensions using four assessmenttechniques: faculty peer ratings,student ratings, self ratings andobjective questionnaires. A com-posite criterion of research cre-ativity was generated from publi-cation records and Science Cita-tion Index counts (first authoredself-citations were excluded). Acomposite for teaching effective-ness was created from annual,end-of-course student evaluationdata collected over the 5 years.

Limiting results to only thosetraits with absolute mean coefficientvalues greater than 0.30, the creativeresearcher can be characterized as: am-bitious (aspiring to accomplish difficulttasks, striving, competitive), enduring(willing to work long hours, preserve-ring, unrelenting), seeking definiteness(dislikes ambiguity or uncertainty in in-formation, wants all questions an-swered completely), dominant (at-tempts to control environment, force-ful, decisive), showing leadership (takesinitiative and responsibility for gettingthings done), aggressive (argumenta-tive, threatening, enjoys combat), inde-pendent (avoids restraints, enjoys be-ing unattached), not meek (not mildmannered, not subservient) andnon-supportive. Eleven traits loaded0.30 or higher characterize effectiveteacher as: liberal (progressive, seekschange, modern, adaptable), sociable(friendly, outgoing, enjoys being withpeople), showing leadership, extra-verted (has many friends, craves excite-ment, fond of practical jokes, is care-free, easy-going, optimistic), low inanxiety (not tense, easy), objective(just, fair, free of bias), supportive(gives sympathy and comfort, helpful,indulgent), non-authoritarian (not

rigid, flexible, not dogmatic, not opin-ionated), not defensive (not suspicious,not guarded, not touchy), intelligent(bright, quick clever) and aestheticallysensitive.

In addition to these replicated traits,the researchers also tend to be low insociability, intelligent, curious, compul-sive (meticulous, perfectionistic, con-cerned with details), orderly, not seek-ing of help, not fun loving, authoritar-ian, defensive, and non-neurotic (not aworrier, not overly emotional, not anx-ious, not moody, not often depressed).Similarly, other traits found for the ef-fective teacher included fun loving,changeable (flexible, restless, likes newand different experiences), low in har-mavoidance (careful, cautious, paina-voident), low in neuroticism, intellectu-ally curious (seeks understanding, re-flective), enduring, orderly, attentionseeking (enjoys being conspicious, dra-matic, colorful), ambitious, non-impul-sive (not spontaneous, not hasty, notimpetuous, inhibited), and approvalseeking (desires to be held in high es-teem, obliging, agreeable).

These results suggest that the con-stellation of traits defining the creativeresearcher and the effective teacher are

approximately orthogonal!While the one cluster suggest in-dependence, achievement orien-tation, dominance, and strivingto create cognitive order, theother denotes an easier-going,intelligent liberality. The onlytrait that effective researchersand teachers shared in commonwas leadership. The one onwhich researchers and teacherswere exactly the opposite wassupportingness, with effectiveresearchers being low and effec-tive teachers high. However, inspite of a fairly clear personalprofile that emerges for both ef-fective researchers and teachersno one shoud think that all effec-tive researchers and teachersconform to these profiles. For ex-ample, although many scientistshave historically been recognizedas less sociable than average, ex-ceptions can be found (e.g.Leibnitz). Also, one should bearin mind that in correlationalstudies it is usually impossible tospecify clear causality. One possi-bility is that success and rein-forcement at teaching or re-

search fosters the "teacher or re-searcher personality".

Many of the personality traits impli-cated here appear to have substantialheritabilities associated with them, tobe noticeable at an early age, and havelong term stability over the life-span. Inother words, personality may con-strain, or predispose one to a certainkind of academic life. To deny a highlyaffiliative person his or her sociabilityfor long hours alone in the laboratorymay be more difficult than similar pro-scriptions for a less sociably inclined,more independently tempered col-league. Similarly, it may well be harderfor the ambitious, task oriented personseeking ultimated definiteness, tospend long hours helping and counsel-ling students than for his or her lessrigid, more nurturant colleagues. Inconclusion, despite the imperfectionsof measures of personality traits, mean-ingful and replicable empirical associa-tions among these measures in suc-cessful university researchers andteachers can be clearly demonstrated.

Goran [imi}

Illustration: Milan Rado{

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Whither GABA?Kre{imir Krnjevi}, McGill University, Montréal QC H3G 1Y6, Canada.

KRE[IMIR KRNJEVI] – BIOGRAPHICAL SKETCH

Was born in Zagreb (1927); completed medical studies at University of Edinburgh (MBChB, 1949), then obtained PhD inPhysiology in 1953 (under D. Whitteridge). Spent two post-doctoral years at University of Washington (Seattle) and anothertwo at Australian National University in Canberra (with John Eccles - later Sir John and Nobel laureate in 1963); finally return-ing to Britain to a position at Babraham Institute (near Cambridge). There began iontophoretic studies on neurotransmittersin the brain, which led to first proposal (in 1963) that the main transmitters are glutamate, for fast excitation, and GABA, forinhibition. In 1964, came to Montreal as visiting professor in physiology at McGill University; where he remained as head ofAnaesthesia Research departement – also Chairman of Physiology department (1978-1987) – until retirement in 2000 (since2001, Emeritus professor of Physiology). Main research topics on functional role in brain of synaptic transmitters (glutamate,GABA and glycine) and modulators (especially acetylcholine), intraneuronal free calcium and K conductance, general anaes-thetics, and lack of oxygen or glucose resulted in over 300 papers: in 1984, was rated one of the ”1000 most-cited contempo-rary authors” (Current Contents). He became a Fellow of the Royal Society of Canada (1975) and Officer of the Order of Can-ada (1987); and received several major awards, including the Gairdner Foundation International Prize (1984), Wilder PenfieldPrize (1997) and the Spiridion Brusina Award (2001).

Montréal February 14, 2005

ABSTRACT of LECTURE FOR ’INSTITUTE ANNIVERSARY DAY’(Zagreb, 16 March 2005)

Fifty years after it was firstconsidered a serious candidate for therole of main chemical transmitter atinhibitory synapses in the brain (1),GABA (�-aminobutyric acid) is as po-pular a topic for research as ever. Wellover 2000 papers dealing with variousaspects of GABAergic function, phar-macology and relevant clinical appli-cations are appearing annually (Med-line). How did this come about andwhere is all this activity leading?GABA’s inhibitory action became clearwhen it was found to increase the Cl-

conductance of cortical neurons (2). Asvarious specific markers and pharma-cological antagonists became available(3), GABAergic synapses could bereadily identified and sudied in greaterdetail. They proved to be widespreadthroughout the central nervous system,accounting for about one third of allsynapses, evidently playing a crucial ro-le in controlling neuronal activity. Theoriginal picture of a straightforwardhyperpolarizing mechanism of inhi-bition – that simply countered the de-polarizing action of glutamatergicsynapses – was interesting enough; butit would not have led to the laterenormous expansion of studies onGABA. Several unexpected findingsrevealed a far more complicated storyand opened up many new fields ofresearch. In the first place, GABA wasfound to act on two quite different

types of receptors: in addition to the Cl-

conductance activating GABAA recep-tor, the GABAB receptor (4) caused aslower G-protein-mediated increase inK+ conductance, marked depression ofGABA (and other tranmitter) release,and activation of the cAMP internalsignalling pathway. This was just thebeginning. The GABAA receptor turnedout to have several allosteric bindingsites, where a wide range of drugs canstrongly enhance GABA’s synapticaction : notably benzodiazepines, ge-neral anaesthetics, alcohol, and someendogenous progesterone-related hor-mones. The obvious clinical relevanceof powerful anxiolytic, anaesthetic andanticonvulsant actions led to a vastexpansion of pharmacotherapeutic stu-dies. Another unexpected discovery,that GABA is a depolarizing agentduring fetal and early post-natal life (5)has thrown new light on its role asmajot excitatory transmitter and tri-gger for neuronal and synaptic develo-pment. Because the action of GABA ismediated by transmembrane Cl- flux,whether it is hyperpolarizing or depo-larizing depends on the direction of Cl-

transport and the age-related predo-minance of specific transporters (6). Inaddition to these new topics, powerfulnew tools are fast expanding the rangeof possible investigations, especially atthe molecular level. Cloning therelevant receptors, enzymes and

transporters has revealed a greatnumber of subtypes; which, albeit furt-her complicating the picture, accountfor site and/or individual-specificvariations in functional properties andmay lead to more selective pharma-cology, that is likely to be of greatbenefit for clinical and research pur-poses (7). Such tools, including therapidly increasing availability of trans-genic animals under- or over-expre-ssing selected genes, are also providingmuch information on factors that de-termine the clustering of GABA rece-ptors and the specific somatic ordendritic location of synapses made byaxons of various types of GABAergicinterneurons. With research continuallyexpanding in these various directions,the story of GABA is still far fromreaching a final conclusion.

1) K Krnjevi} & JW Phillis, (1963) J.Physiol. Lond. 165: 274.

2) K Krnjevi} & S Schwartz, (1967)Exp. Brain Res. 3: 320.

3) DR Curtis, AW Duggan, D. Felix &GA Johnston, (1970) Nature 226:1222.

4) NG Bowery, DR Hill et al. (1980)Nature. 283: 92. .

5) E Cherubini, JL Gaiarsa, Y Ben-Ari,(1991) Trends Neurosci. 14: 515.

6) E Delpire, (2000) News Physiol.Sci. 15: 309.

7) NG Bowery, SJ Enna & RW Olsen(2004) Biochem Pharmacol 68:1477.

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Croatian Institutefor Brain Research Publications1997 – 2004

1997-2001In the 1997 – 2001 period, researchers at the Croatian Institute for Brain Research (CIBR) were engaged in the realization of

CIBR's first Program project entitled «Neurobiology of Cognitive Development and Cognitive Disorders». That program projectconsisted of 22 individual research projects (17 senior researcher projects + 5 young investigator award projects), groupedinto three main program themes:

Theme A: Neurobiology of normal and disturbed brain development: recovery and plasticity after lesion (11 projects)Theme B: Neurobiology of neurological and mental disorders with cognitive disturbances (8 projects)Theme C: Molecular pharmacology of behavior and biochemistry of neurotransmitters and second messengers (4 projects)The publications listed below are arranged in the same way (themes A, B, and C) and listed chronologically. However, to en-

hance the browsing we included headlines denoting major research areas. We have listed exclusively original articles and re-views published in peer-reviewed journals cited in Current Contents and PubMed/Medline online databases. Names printedin bold denote group leaders or principal investigators of individual research projects (for overview of project titles and prin-cipal investigators, click here). A selected list of other publications of the CIBR's faculty (not directly related to our programproject) is provided under the heading «Other publications».

THEME A:

Developmental Neuroscience& Genetics of development:

Letini} K, Kostovi} I (1997) Transient fetalstructure, the gangliothalamic body, con-nects telencephalic germinal zone with allthalamic regions in the developing humanbrain. J Comp Neurol 384(3):373-395.

Delalle I, Evers P, Kostovi} I, Uylings HB(1997) Laminar distribution of neuropeptideY-immunoreactive neurons in human pre-frontal cortex during development. J CompNeurol 379(4):515-522.

Gajovi} S, St-Onge L, Yokota Y, Gruss P(1997) Retinoic acid mediates Pax6 expres-sion during in vitro differentiation of embry-onic stem cells. Differentiation 62(4):187-192.

Gajovi} S, Chowdhury K, Gruss P (1998)Genes expressed after retinoic acid-medi-ated differentiation of embryoid bodies arelikely to be expressed during embryo devel-opment. Exp Cell Res 242(1):138-143.

Gajovi} S, Gruss P (1998) Differentiationof the mouse embryoid bodies grafted onthe chorioallantoic membrane of the chickembryo. Int J Dev Biol 42(2):225-228.

Heffer-Lauc M, ^a~i} M, [erman D (1998)C-series polysialogangliosides are expressedon stellate neurons of adult human cerebel-lum. Glycoconjugate J 15(4):423-426.

Kru{lin B, Juki} S, Kos M, [imi} G, Cviko A(1998) Congenital anomalies of the centralnervous system at autopsy in Croatia in theperiod before and after the Chernobyl acci-dent. Acta Med Croat 52(2):103-107.

Terzi} J, Muller C, Gajovi} S, Saraga-Babi} M(1998) Expression of PAX2 gene during humandevelopment. Int J Dev Biol 42(5):701-707.

Letini} K, Kostovi} I (1998) Postnatal de-velopment of calcium-binding proteins cal-

bindin and parvalbumin in human visualcortex. Cereb Cortex 8(7):660-669.

Letini} K, Heffer-Lauc M, Rosner H, Ko-stovi} I (1998) C-pathway polysialoganglio-sides are transiently expressed in the humancerebrum during fetal development. Neuro-science 86(1):1-5.

Kostovi} I, Juda{ M (1998) Transient pat-terns of organization of the human fetalbrain. Croat Med J 39(2):107-114.

Juda{ M, [estan N, Kostovi} I (1999)Nitrinergic neurons in the developing andadult human telencephalon: transient andpermanent patterns of expression in compar-ison to other mammals. Microsc Res Techn45(6):401-419.

[imi} G, Mrzljak L, Fu~i} A, Winblad B,Lovri} H, Kostovi} I (1999) Nucleus sub-putaminalis (Ayala): the still disregardedmagnocellular component of the basal fore-brain may be human specific and connectedwith the cortical speech area. Neuroscience89(1):73-89.

Marro ML, Scremin OU, Jordan MC, HuynhL, Porro F, Roos KP, Gajovi} S, Baralle FE, MuroAF (2000) Hypertension in beta-adducin-de-ficinet mice. Hypertension 36(3):449-453.

Murro AF, Marro ML, Gajovi} S, Porro F,Luzzatto L, Baralle FE (2000) Mild spherocytichereditary elliptocytosis and altered levels ofalpha- and gamma-adducins in beta-addu-cin-deficient mice. Blood 95(12):3978-3985.

Pediatric Neurology& Fetal/Perinatal Physiology:

Meja{ki-Bo{njak V, Be{enski N (1997)Megalencephalic leukoencephalopathy: afurther case of a new neurodegenerativewhite matter disease. Dev Med Child Neurol39(8):561-563.

Meja{ki-Bo{njak V, Be{enski N, Brock-mann K, Pouwels PJ, Frahm J, Hanefeld FA(1997) Cystic leukoencephalopathy in amegalencephalic child: clinical and mag-netic resonance imaging/magnetic reso-nance spectroscopy findings. Pediatr Neurol16(4):347-350.

Arbeille P, Maulik D, Salihagi} A, LocatelliA, Lansac J, Platt LD (1997) Effect oflong-term cocaine administration to preg-nant ewes on fetal hemodynamics, oxygena-tion, and growth. Obstet Gynecol90(5):795-802.

Kurjak A, Kupe{i} S, Hafner T, Kos M, Ko-stovi}-Kne`evi} Lj, Grbe{a D (1997) Con-flicting data on intervillous circulation in earlypregnancy. J Perinat Med 25(3):225-236.

^a~i} M, Wilichowski E, Meja{ki-Bo{njakV, Fumi} K, Luji} L, Maru{i} Della Marina B,Hanefeld V (2001) Cytochrome c oxidasepartial deficiency-associated Leigh diseasepresenting as an extrapyramidal syndrome. JChild Neurol 16(8):616-619.

Leegwater PA, Yuan BQ, van der Steen J,Mulders J, Konst AA, Boor PK, Meja-{ki-Bo{njak V, van der Maarel SM, FrantsRR, Oudejans CB, Schutgens RB, Pronk JC,van der Knaap MS (2001) Mutations ofMCL1 (KIAA0027), encoding a putativemembrane protein, cause megalencephalicleukoencephalopathy with subcortical cysts.Am J Hum Genet 68(4):831-838.

Habek D, Hodek B, Herman R, Mati~evi} A,Jugovi} D, Habek JC, Salihagi} A (2001)Modified fetal biophysical profile in the as-sessment of perinatal outcome. Zentralblattfür Gynaecologie 123(7):411-414.

Neurosurgery& CSF Pathophysiology:

Melada A, Paladino J, Mikli} P, Ivekovi} V(1997) Use of intraoperative ultrasound in

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neurosurgery (in Croatian). Lijec Vjesn119(11-12):331-336.

Rotim K, Mikli} P, Paladino J, Melada A,Marciki} M, [}ap M (1997) Reducing the in-cidence of infection in pediatric cerebro-spinal fluid shunt operations. Childs NervousSystem 13(11-12):584-587.

Vladi} A, Striki} N, Jur~i} D, Zmajevi} M,Klarica M, Bulat M (2000) Homeostatic roleof the active transport in elimination of(3H)benzylpenicillin out of the cerebrospinalfluid system. Life Sci 67(19):2375-2385.

Ore{kovi} D, Klarica M, Vuki} M (2001)Does the secretion and circulation of thecerebrospinal fluid really exist? Med Hypoth-eses 56(5):622-624.

THEME B:

Psychiatry& Molecular Neuropharmacology:

Marcusson J, Rother M, Kittner B, RossnerM, Smith RJ, Babi} T, Folnegovi}-[malc V,Moller HJ, Labs KH (1997) A 12-month, ran-domized, placebo-controlled trial ofpropentofylline (HWA 285) in patients withdementia according to DSM III-R. The Euro-pean Propentofylline Study Group. Demen-tia & Geriatric Cognitive Disorders8(5):320-328.

Henigsberg N, Lagerkvist B, Matek Z,Kostovi} I (1997) War victims in need ofphysical rehabilitation in Croatia. Scand JSoc Med 25(3):202-206.

Trkulja V, Lackovi} Z (1997) Ecstasy (inCroatian). Lijec Vjesn 119(5-6):158-166.

Nankai M, Klarica M, Fage D, Carter C(1998) The pharmacology of nativeN-methyl-D-aspartate receptor subtypes:different receptors control the release of dif-ferent striatal and spinal transmitters. ProgNeuro-Psychopharmacol Biol Psychiatr2281):35-64.

Jernej B, Hranilovi} D, ^i~in-[ain L (1998)Serotonin transporter on rat platelets: levelsof mRNA underlie inherited differences in up-take kinetics. Neurochem Int 33(6):519-522.

^i~in-[ain L, Frobe A, Jernej B (1998) Physi-ological characteristics of serotonin transport-ers on rat platelets. Comp Biochem Physiol A(Mol Integr Physiol) 120(4):723-729.

Romero L, Jernej B, Bel N, ^i~in-[ain L,Cortes R, Artigas F (1998) Basal and stimu-lated extracellular serotonin concentrationin the brain of rats with altered serotoninuptake. Synapse 28(4):313-321.

Trkulja V, Lackovi} Z (1999) Addictivesubstances and medical students in Zagreb(in Croatian). Lijec Vjesn 121(4-5):115-117.

^i~in-[ain L, Mimica N, Hranilovi} D, BalijaM, Ljubin T, Makari} G, Folnegovi}-[malcV, Jernej B (2000) Posttraumatic stress dis-order and platelet serotonin measures. JPsychiatr Res 34(2):155-161.

DeLisi LE, Razi K, Stewart J, Relja M,Shields G, Smith AB, Wellman N, Larach VW,Loftus J, Vita A, Comazzi M, Crow TJ (2000)No evidence for a parent-of-origin effect de-tected in the pattern of inheritance ofschizophrenia. Biol Psychiatr 48(7):706-709.

Jernej B, Banovi} M, ^i~in-[ain L, Hra-nilovi} D, Balija M, Ore{kovi} D, Folnego-vi}-[malc V (2000) Physiological character-istics of platelet/circulatory serotonin: studyon a large human population. Psychiatr Res94(2):153-162.

Kozari}-Kova~i} D, Ljubin T, Ruti}-Pu` L,Mihaljevi} J, Jernej B, ^i~in-[ain L (2000)Platelet monoamine oxidase activity, egostrength, and neuroticism in soldiers withcombat-related current posttraumatic stressdisorder. Croat Med J 41(1):76-80.

Ljubin T, @aki} Milas D, Mimica N, Fol-negovi}-[malc V, Makari} G (2000) A pre-liminary study of the comparative effects ofolanzapine and fluphenazine on cognitionin schizophrenic patients. Hum Psychophar-macol 15(7):513-519.

Lichtermann D, Hranilovi} D, Trixler M,Franke P, Jernej B, Delmo CD, Knapp M,Schwab SG, Maier W, Wildenauer DB (2000)Support for allelic association of a polymor-phic site in the promoter region of the seroto-nin transporter gene with risk for alcohol de-pendence. Am J Psychiatr 157(12):2045-2047.

[tefulj J, Jernej B, ^i~in-[ain L, Rinner I,Schauenstein K (2000) mRNA expression ofserotonin receptors in cells of the immunetissues of the rat. Brain Behav Immun14(3):219-224.

Hranilovi} D, Schwab SG, Jernej B, KnappM, Lerer B, Albus M, Rietschel M, Kanyas K,Borrmann M, Lichtermann D, Maier W,Wildenauer DB (2000) Serotonin transportergene and schizophrenia: evidence for associ-ation/linkage disequilibrium in families withaffected siblings. Mol Psychiatr 5(1):91-96.

Hranilovi} D, Herak-Kramberger CM,^i~in-[ain L, Saboli} I, Jernej B (2001) Seroto-nin transporter in rat platelets. Level of pro-tein expression underlies inherited differ-ences in uptake kinetics. Life Sci 69(1):59-65.

Henigsberg N, Folnegovi}-[malc V, MoroL (2001) Stressor characteristics andpost-traumatic stress disorder symptom di-mensions in war victims. Croat Med J42(5):543-550.

Mimica N, Folnegovi}-[malc V, Folnego-vi} Z (2001) Catatonic schizophrenia inCroatia. Eur Arch Psychiatr Clin Neurosci251(Suppl 1):117-120.

[tefulj J, ^i~in-[ain L, Schauenstein K,Jernej B (2001) Serotonin and immune re-sponse: effect of the amine on in vitro prolif-eration of rat lymphocytes. Neuroim-munomodulation 9(2):103-108.

Neurology & Neuropathology:

Zurak N (1997) Role of the supra-chiasmatic nucleus in the pathogenesis of mi-graine attacks. Cephalalgia 17(7):723-728.

[imi} G, Kostovi} I, Winblad B, Bog-danovi} N (1997) Volume and number ofneurons of the human hippocampal forma-tion in normal aging and Alzheimer's dis-ease. J Comp Neurol 379(4):482-494.

Panula P, Rinne J, Kuokkanen K, ErikssonKS, Sallmen T, Kalimo H, Relja M (1998)Neuronal histamine deficit in Alzheimer'sdisease. Neuroscience 82(4):993-997.

Kor{i} M, @arkovi} K, @arkovi} N, Plav{i}V, Paladino J, [kori} T, Aganovi} I, Ko-zi}-Rukavina B, Giljevi} Z, Perkovi} Z,

Breskovac L, Melada A, Pirker N (1998) Aclinico-experimental study of the functionalmorphology of hypophyseal adenomas (inCroatian). Lijec Vjesn 120(9):262-273.

[kori} T, Kor{i} M, @arkovi} K, Plav{i} V,Be{enski N, Breskovac L, Giljevi} Z, Paladino J(1999) Clinical and morphological featuresof undifferentiated monomorphousGH/TSH-secreting pituitary adenoma. Eur JEndocrinol 140(6):528-537.

@arkovi} N, @arkovi} K, Schaur RJ, Stolc S,Schlag G, Redl H, Waeg G, Borovi} S, Lon-~ari} I, Juri} G, Hlavka V (1999) 4-Hy-droxynonenal as a second messenger of freeradicals and growth modifying factor. LifeSci 65(18-19):1901-1904.

Babi} T, Zurak N (1999) Convulsions in-duced by donepezil. J Neurol NeurosurgPsychiat 66(3):410.

Babi} T, Banfi} L, Papa J, Bari{i} N, Jelin~i} Z,Zurak N (2000) Spontaneous rupture of oe-sophagus (Boerhaave's syndrome) related torivastigmine. Age & Ageing 29(4):370-371.

[imi} G, [e{o-[imi} D, Lucassen PJ, IslamA, Krsnik @, Cviko A, Jela{i} D, Bari{i} N,Winblad B, Kostovi} I, Kru{lin B (2000)Ultrastructural analysis and TUNEL demon-strate motor neuron apoptosis inWerdnig-Hoffmann disease. J NeuropatholExp Neurol 59(5):398-407.

[imi} G, Lucassen PJ, Krsnik @, Kru{lin B,Kostovi} I, Winblad B, Bogdanovi} N (2000)NOS expression in reactive astrocytes corre-lates with increased cell death related DNAdamage in the hippocampus and entorhinalcortex in Alzheimer's disease. Exp Neurol165(1):12-26.

Canki-Klain N, Recan D, Mili~i} D, Llense S,Leturcq F, Deburgrave N, Kaplan JC, DebevecM, Zurak N (2000) Clinical variability and mo-lecular diagnosis in a four-generation familywith X-linked Emery-Dreifuss muscular dys-trophy. Croat Med J 41(4):389-395.

Stefanovi} M, Topi} E, Ivani{evi} AM,Relja M, Kor{i} M (2000) Genotyping ofCYP2D6 in Parkinson's disease. Clin ChemLab Med 38(9):929-934.

Zurak N (2000) Nervous system in thefibrillar theory of Giorgio Baglivi. MedicinaNei Secoli 12(1):147-158.

@arkovi} N, Hayn M, Tatzber F, Reichel H,Kor{i} M, @arkovi} K, Plav{i} V, Breskovac LJ,Klingmuller M, Paladino J (2000) Growthpromoting effect of human plasma ultra-filtrate bioactive fraction (TBP) for humannon-functioning pituitary adenoma cells invitro. J Endocrinol Invest 23(11):737-743.

Pentz-Vidovi} I, [kori} T, Grubi{i} G,Kor{i} M, Ivi~evi}-Bakuli} T, Be{enski N, Pa-ladino J, Plav{i} V, @arkovi} K (2000) Evolu-tion of clinical symptoms in a young womanwith a recurrent gonadotroph adenomacausing ovarian hyperstimulation. Eur JEndocrinol 143(5):607-614.

Kor{i} M, Plav{i} V, Be{enski N, [kori} T,Giljevi} Z, @arkovi} K, @arkovi} N, Zaninovi}L, Paladino J, Aganovi} I (2001) Importanceof the CRH (corticotropin releasing hor-mone) test in the differential diagnosis ofCushing's syndrome (in Croatian). LijecnVjesn 123(7):165-168.

Sovi} A, Borovi} S, Lon~ari} I, Kreuzer T,@arkovi} K, Vukovi} T, Wag G, Hra{~an R,Wintersteiger R, Klinger R, Zurak N, Schaub

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RJ, @arkovi} N (2001) The carcinostatic andproapoptotic potential of 4-hydroxynonenalin HeLa cells is associated with its conjuga-tion to cellular proteins. Anticancer Res21(3B):1997-2004.

Neuroimaging & Radiology:

Huang M, Aine CJ, Supek S, Best E,Ranken D, Flynn ER (1998) Multi-start down-hill simplex method for spatio-temporalsource localization in magnetoencephalo-graphy. Electroencephalography & ClinicalNeurophysiology 108(1):32-44.

Hebrang A, [imuni} S, Be{enski N, TurekS (1998) Methodology of renovation ofradiologic equipment in the Republic ofCroatia. European Radiology 8(1):153-155.

Supek S, Aine CJ, Ranken D, Best E, FlynnER, Wood CC (1999) Single vs. paired visualstimulation: superposition of early neuro-magnetic responses and retinotopy inextrastriate cortex in humans. Brain Res830(1):43-55.

Jankovi} S, Be{enski N, Bu{i} Z, Duji} Z,Buca A, Ma{kovi} J, Lu{i} I, Primorac D(2000) Craniocerebral war missile injuries:clinical and radiological study. ActaNeurochirurgica 142(1):101-102.

Kova~i} L, Lon~ari} S, Paladino J, Kern J(2000) The Croatian telemedicine. Studies inHealth Technology & Informatics77:1146-1150.

Klapan I, Barbir A, [imi~i} L, Ri{avi R,Be{enski N, Bumber Z, Stiglmayer N, Antoli}S, Janjanin S, Bili} M (2001) Dynamic 3Dcomputer-assisted reconstruction of a me-tallic retrobulbar foreign body for diagnosticand surgical purposes (Case report of orbitalinjury with ethmoid bone involvement). Or-bit 20(1):35-49.

THEME C:

Signaling mechanisms& Second messengers:

Beara-Lasi} L, Knotek M, ^ejvan K, Jak{i}O, Lasi} Z, [kori} B, Brklja~i} V, Banfi} H(1997) The effect of big endothelin-1 in theproximal tubule of the rat kidney. Br JPharmacol 120(4):625-630.

Divecha N, Banfi} H, Treagus JE, Vann L,Irvine RF, D'Santos C (1997) Nucleardiacylglycerol, the cell cycle, the enzymesand a red herring (or how we came to lovephsophatidylcholine). Biochem Soc Trans25(2):571-575.

Haberstock-Debic H, Banfi} H, Stevens WJ,De Clerck LS, Wechsung E, De Potter W (1997)Stimulation of T-cell proliferation by pancrea-statin and its C-terminal fragment (33-49).Neuroimmunomodulation 4(5-6):244-249.

Vi{nji} D, Batini} D, Banfi} H (1997)Arachidonic acid mediates interfe-ron-gamma-induced sphingomyelin hydro-lysis and monocytic marker expression inHL-60 cell line. Blood 89(1):81-91.

Banfi} H, Downes CP, Rittenhouse SE(1998) Biphasic activation of PKBalpha/Aktin platelets. Evidence for stimulation both by

phosphatidylinositol 3,4-bisphosphate, pro-duced via a novel pathway, and by phospha-tidylinositol 3,4,5-trisphosphate. J BiolChem 273(19):11630-7.

Zhang J, Banfi} H, Straforini F, Tosi L,Volinia S, Rittenhouse SE (1998) A type IIphosphoinositide 3-kinase is stimulated viaactivated integrin in platelets. A source ofphosphatidylinositol 3-phosphate. J BiolChem 273(23):14081-14084.

Vi{nji} D, Batini} D, Banfi} H (1999) Differ-ent roles of protein kinase C alpha and deltaisoforms in the regulation of neutralsphingomyelinase activity in HL-60 cells.Biochem J 344(Pt 3):921-928.

Markoti} A, Lumen R, Maru{i} A, Jonji} S,Müthing J (1999) Ganglioside expression intissues of mice lacking the tumor necrosisfactor receptor 1. Carbohydrate Res321(1-2):75-87.

Gr~evi} D, Lee SK, Maru{i} A, Lorenzo JA(2000) Depletion of CD4 and CD8 T lympho-cytes in mice in vivo enhances 1,25-di-hydroxyvitamin D3-stimulated osteoclast-likecell formation in vitro by a mechanism that isdependent on prostaglandin synthesis. JImmunol 165(8):4231-4238.

Gr~evi} D, Katavi} V, Luki} IK, Kova~i} N,Lorenzo JA, Maru{i} A (2001) Cellular andmolecular interactions between immunesystem and bone (review). Croat Med J42(4):384-392.

Knotek M, Jak{i} O, Malnar M, Banfi} H(2001) Endothelin mediates phospholipaseC stimulation in the proximal tubule duringinitiation of compensatory renal growth inadult rats. Croat Med J 42(5):506-510.

Sin|i} A, Aleksandrova A, Fields AP,Volinia S, Banfi} H (2001) Presence and acti-vation of nuclear phosphoinositide 3-kinaseC2beta during compensatory liver growth. JBiol Chem 276(21):17754-17761.

Traven A, Wong JM, Xu D, Sopta M,Ingles CJ (2001) Interorganellar communica-tion. Altered nuclear gene expression pro-files in a yeast mitochondrial DNA mutant. JBiol Chem 276(6):4020-4027.

Trkulja V, Lackovi} Z (2001) Vagal influ-ence on compensatory ovarian growth is im-portant only briefly after hemicastration.Exp Biol Med (Maywood) 226(8):776-781.

Vukeli} Z, Kalanj-Bognar S (2001) Celldensity-dependent changes ofglycosphingolipid biosynthesis in culturedhuman skin fibroblasts. Glycoconjugate J18(6):429-437.

Behavioral Neuropharmacology:

Peri~i} D, Bujas M (1997) Sex differences inbicuculline-induced convulsions: interactionwith stress and ligands of benzodiazepinebinding sites. Brain Res 752(1-2):279-284.

Peri~i} D, Bujas M (1997) Sex differencesin the response to GABA antagonists de-pend on the route of drug administration.Exp Brain Res 115(1):187-190.

Bujas M, Peri~i} D, Jazvin{}ak M (1997)Influence of gender and gonadectomy onbicuculline-induced convulsions and onGABA-A receptors. Brain Res Bull43(4):411-416.

Bujas M, Tvrdei} A, Peri~i} D (1997) Re-gional differences in NaCl-induced increase

of the potency of bicuculline to displace(3H)muscimol binding. Neurochem Int30(2):199-202.

Peri~i} D, Mirkovi} K, Jazvin{}ak M,Besnard F (1998) (3H)t-butylbicyclo-orthobenzoate binding to recombinantalpha1beta2gamma2s GABA(A) receptor.Eur J Pharmacol 360(1):99-104.

Peri~i} D, Bujas M, Mirkovi} K, Jazvin{}akM (1999) Effects of adrenalectomy andgonadectomy on sex and stress-induced dif-ferences in bicuculline-induced convulsions.Exp Brain Res 129(3):451-456.

Peri~i} D, Jazvin{}ak M, [vob D, Mirkovi}K (2000) Beta-1 adrenoceptor antagonistspotentiate the anticonvulsive effect of swimstress in mice. Pharmacol Biochem Behav67(3):507-510.

Peri~i} D, [vob D, Jazvin{}ak M, Mirkovi}K (2000) Anticonvulsive effect of swim stressin mice. Pharmacol Biochem Behav66(4):879-886.

Peri~i} D, Jazvin{}ak M, Mirkovi} K (2001)(3H)Flunitrazepam binding to recombinantalpha1beta2gamma2S GABA(A) receptorsstably expressed in HEK 293 cells. BiomedPharmacother 55(4):221-228.

Peri~i} D, Jazvin{}ak M, [vob D, Mirkovi}K (2001) Swim stress alters the behaviouralresponse of mice to GABA-related and someGABA-unrelated convulsants. Epilepsy Res43(2):145-152.

Peri~i} D, [vob D, Jazvin{}ak-Jembrek M,Mirkovi}-Kos K (2001) The involvement ofalpha2-adrenoceptors in the anticonvulsiveeffect of swim stress in mice. Psychophar-macology (Berl) 158(1):87-93.

OTHER PUBLICATIONS –CYTOGENETICS& MEDICAL GENETICS:

Schinzel A, Braegger CP, Bre~evi} L, DutlyF, Binkert F (1997) Interstitial deletion,del(4)(q12q21.1), owing to de novo unbal-anced translocation in a 2 year old girl: fur-ther evidence that the piebald trait maps toproximal 4q12. J Med Genet 34(8):692-695.

Schinzel A, Bre~evi} L, Dutly F, Baumer A,Binkert F, Largo RH (1997) Multiple congeni-tal anomalies including the Rieger eye mal-formation in a boy with interstitial deletionof (4)(q25-->q27) secondary to a balancedinsertion in his normal father: evidence forhaplotype insufficiency causing the Riegermalformation. J Med Genet34(12):1012-1014.

Schinzel A, Kotzot D, Bre~evi} L, Robin-son WP, Dutly F, Dauwerse H, Binkert F,Baumer A, Ausserer B (1997) Trisomy first,translocation second, uniparental disomyand partial trisomy third: a new mechanismfor complex chromosomal aneuploidy. Eur JHum Genet 5:308-314.

Schrimpf SP, Bleiker AJ, Bre~evi} L, KozlovSV, Berger P, Osterwalder T, Krueger SR,Schinzel A, Sonderegger P (1997) Humanneuroserpin (PI12): cDNA cloning and chro-mosomal localization to 3q26. Genomics40(1):55-62.

Cekada S, Kilvain S, Brajenovi}-Mili} B,Bre~evi} L, Kirini-Paui E, Franulovi} J (1999)Partial trisomy 13q22->qter and monosomy18q21-->ter as a result of familialtranslocation. Acta Paediatr 88:675-678.

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Chrzanowska KH, Krajewska-Walasek M, KuJ, Michakiewicz J, Maziarka D, Wolski JK,Bre~evi} L, Madaliski K (1998) Kabuki(Niikawa-Kuroki) syndrome associated withimmunodeficiency. Clin Genet 53(4):302-312.

Fokstuen S, Arbenz U, Artan S, Dutly F,Bauersfeld U, Bre~evi} L, Fasnacht M,Röthlisberger B, Schinzel A (1998) 22q11.2deletions in a series of patients with non-se-lective congenital heart defects: incidence,type of defects and parental origin. ClinGenet 53(1):6-9.

Utkus A, Sorokina I, Kucinskas V,Röthlisberger B, Balmer D, Bre~evi} L,Schinzel A (1999) Duplication of segment1p21 following paternal insertionaltranslocation, ins(6;1) (q25;p13.3p22.1). JMed Genet 36(1):73-76.

Riegel M, Castellan C, Balmer D, Bre~evi}L, Schinzel A (1999) Terminal deletion,del(1)(p36.3), detected through screeningfor terminal deletions in patients with un-classified malformation syndromes. Am JMed Genet 29(82:3):249-253.

Röthlisberger B, Kotzot D, Bre~evi} L,Koehler M, Balmer D, Binkert F, Schinzel A(1999) Recombinant balanced and unbal-anced translocations as a consequence of abalanced complex chromosomal rearrange-ment involving eight breakpoints in fourchromosomes. Eur J Hum Genet7(8):873-883.

Bre~evi} L, Basaran S, Dutly F,Rothlisberger B, Schinzel A (2000) Tandemtriplication of chromosome 13q14 with in-verted interstitial segment in a 4 year oldgirl. J Med Genet 37(12):964-967.

Gebhart E, Verdorfer I, Saul W, TrautmannU, Bre~evi} L (2000) Delimiting the use ofcomparative genomic hybridization in hu-man myeloid neoplastic disorders. Int JOncol 16(6):1099-1105.

Frascella E, Lenzini E, Schafer BW,Bre~evi} L, Dorigo E, Toffolatti L, Nanni P,De Giovanni C, Rosolen A (2000) Concomi-tant amplification and expression ofPAX7-FKHR and MYCN in a humanrhabdomyosarcoma cell line carrying a cryp-tic t(1;13)(p36;q14). Cancer GenetCytogenet 121(2):139-145.

Kotzot D, martinez MJ, Bagci G, BasaranS, Baumer A, Binkert F, Bre~evi} L, CastellanC, Chrzanowska K, Dutly F, Gutkowska A,Karaüzüm SB, Krajwska-Walasek M, LuleciG, Miny P, Riegel M, Schuffenhauer S, SeidelH, Schinzel A (2000) Parental origin andmechanisms of formation of cytogeneticallyrecognizable de novo direct and invertedduplications. J Med Genet 37(4):281-286.

Bre~evi} L, Verdorfer I, Saul W,Trautmann U, Gebhart E (2001) Thecytogenetic view of standard comparativegenomic hybridization (CGH): deletions of20q in human leukemia as a measure of thesensitivity of the technique. Anticancer Res21(1A):89-92.

Verdorfer I, Bre~evi} L, Saul W, SchenkerB, Kirsch M, Trautmann U, Helm G,Gramatzki M, Gebhart E (2001) Comparativegenomic hybridization-aided unravelling ofcomplex karyotypes in human hemato-poietic neoplasias. Cancer Genet Cytogenet124(1):1-6.

OTHER PUBLICATIONS -PATHOLOGY:

Osmak M, Kapitanovi} S, Vrhovec I,Beketi}-Ore{kovi} L, Jernej B, Eljuga D, Skrk J(1997) Characterization of human breastadenocarcinoma SK-BR-3 cells resistant todoxorubicin. Neoplasma 44(3):157-162.

Kru{lin B, Hra{~an R, Manojlovi} S, Paveli}K (1997) Oncoproteins and tumor suppres-sor proteins in congenital sacrococcygealteratomas. Pediatr Pathol Lab Med17(1):43-52.

Manojlovi} S, Grgurevi} J, Kne`evi} G,Kru{lin B (1997) Glandular odontogeniccyst: a case report and clinicopathologicanalysis of the relationship to centralmucoepidermoid carcinoma. Head Neck19(3):227-231.

Alujevi} A, Juri} G, [eparovi} V, Kru{lin B(1997) Invasive breast carcinoma withgranulomatous stromal response. Zentral-blatt für Gynäkologie 119(7):343-345.

Alujevi} A, Juri} G, [eparovi} R, Kru{lin B(1998) Unusual features of metastatic atypi-cal carcinoid of the larynx. European Archivesof Oto-Rhino-Laryngology 255(6):318-321.

[ar~evi} B, [eparovi} R, [eparovi} V,Ore{i} V, Nola N, Vrdoljak M, Mari} M,[tajcer-[titi} V, Milas I, Kru{lin B (1998)Prognostic value of determination of thepresence and histologic grade of theintraductal component in invasive ductalcarcinoma of the breast after conservativetreatment (in Croatian). Lijec Vjesn120(1-2):4-7.

Kru{lin B, Tomasovi} C, ^upi} H, BeliczaM (1998) Basaloid squamous cell carcinomaof the larynx: report of two cases. Croat MedJ 3984):450-452.

Kru{lin B, Kopjar A, Dimanovski J, BeliczaM (1999) Correlation between vimentin ex-pression and morphological features of re-nal cell carcinoma. Acta Med Croat53(1):11-14.

Cviko A, Mili} Z, ^izmi} A, Seiwerth S,Kru{lin B (1999) Inflammatory myo-fibroblastic tumor with extensive involve-ment of the bowel in a 7-year-old child.Croat Med J 40(4):550-553.

Markovi}-Pua~ L, Relji} A, Kru{lin B (1999)Primary malignant melanoma of the femaleurethra (in Croatian). Lijec Vjesn121(3):98-99.

Hajn`i} TF, Kru{lin B, Belicza M (1999) Ca-rotid body paraganglioma in a nine-year-oldboy with extensive pulmonary metastases.Medical & Pediatric Oncology 32(5):399-400.

Osmak M, Bordukalo T, Jernej B, KosmrljJ, Polanc S (1999) Diazene JK-279: potentialanticancer drug. Anticancer Drugs10(9):853-859.

Osmak M, Bordukalo T, Ristov AA, JernejB, Kosmrlj J, Polanc S (2000) Diazenes asmodificators of drug-resistance in tumorcells. Neoplasma 47(6):390-395.

Manojlovi} S, Aljinovi}-Ratkovi} N,Kru{lin B (2000) Calcified leiomyoma of thelateral pterygoid muscle in an 8-year-oldboy. Oral Surgery Oral Medicine Oral Pathol-ogy Oral Radiology & Endodontics89(2):199-203.

Kru{lin B, Stani} G, Belicza M, ^upi} H,Begi}-Fehir J, Mui} B, Markoja I (2000) Carci-noma of the urinary bladder resemblinglymphoepithelioma (in Croatian). Lijec Vjesn122(11-12):270-272.

Kru{lin B, Vi{nji} A, ^izmi} A, Tomi~i} I,Kos M, Juki} S, Seiwerth S (2000) DNA ploidyanalysis and cell proliferation in congenitalsacrococcygeal teratomas. Cancer89(4):932-937.

Bradamante V, Smigovec E, Bukovi} D,Geber J, Matani} D (2000) Plasmacholinesterase activity in patients with uter-ine cervical cancer during radiotherapy.Collegium Anthropologicum 24(2):373-380.

Gregurek-Novak T, Talan-Hranilovi} J,Troskot N, Vu~i} M, Kru{lin B (2000)Syringoid eccrine carcinoma. J Eur AcadDermatol Venereol 15(2):143-146.

Kru{lin B (2001) Pseudomyxomaperitonei associated with mucinous epithe-lial cysts of the spleen (in Croatian). LijecVjesn 123(5-6):154.

Gulam I, Pegan B, Stan~i} V, Kru{lin B(2001) Langerhans' cell granulomatosis in anadult: a 22-year follow up. Eur ArchOto-Rhino-Laryngol 258(4):203-207.

[eparovi} R, Glumbi} I, Piga~ B, [eparovi}V, Kru{lin B (2001) Parachordoma: a case re-port. Tumori 87(3):207-210.

OTHER PUBLICATIONS – VARIA:Milavec-Pureti} V, Orli} D, Maru{i} A (1998)

Sensitivity to metals in 40 patients with failedhip endoprosthesis. Arch Orthopaed TraumaSurgery 117(6-7):383-386.

Maru{i} A, Kova~i} N, Petrak J (1998)Presenting randomised trial reports. Lancet351(9095):69.

Maru{i} A, Maru{i} M (1998) CroatianMedical Journal and the war. National Medi-cal Journal of India 11(4):190-192.

Maru{i} A, Me{trovi} T, Petrove~ki M,Maru{i} M (1998) Peer review in the Cro-atian Medical Journal from 1992 to 1996.Croat Med J 39(1):3-9.

Maru{i} A, Maru{i} M (1999) Autorshipcriteria and academic reward. Lancet353(9165):1713-1714.

Maru{i} A, Maru{i} M (1999) Small scien-tific journals from small countries: breakingfrom a vicious circle of inadequacy. CroatMed J 40(4):508-514.

Maru{i} A, Katavi} V, Gr~evi} D, Luki} IK(1999) Genetic variability of new bone in-duction in mice. Bone 25(1):25-32.

Zurak N, Dere`i} D, Pavlekovi} G (1999)Students' opinions on the medical ethicscourse in the medical school curriculum. JMed Ethics 25(1):61-62.

Hrgovi} Z, Salihagi} A, Ku{an M (1999)HPV infection of the genital system: newfindings (in Croatian). Lijec Vjesn121(6):198-203.

Jelovac N, Sikiri} P, Ru~man R, Petek M,Marovi} A, Perovi} D, Seiwerth S, Mi{e S,Turkovi} B, Dodig G, Mikli} P, Buljat G,Prka~in I (1999) Pentadecapeptide BPC 157attenuates disturbances induced byneuroleptics: the effect on catalepsy andgastric ulcers in mice and rats. Eur JPharmacol 379(1):19-31.

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Maru{i} A (2000) Factor analysis of riskfor coronary heart disease: an independentreplication. Int J Cardiol 75(2-3):233-238.

Maru{i} M, Martini} Blase E, Maru{i} A(2000) Croatian Medical Journal at the turnof the millenium. Croat Med J 41(1):5-27.

Maru{i} A, Gr~evi} D, Katavi} V, Kova~i}N, Luki} IK, Kalaj`i} I, Lorenzo JA (2000) Roleof B lymphocytes in new bone formation.Lab Invest 80(11):1761-1774.

Kova~i} N, Müthing J, Maru{i} A (2000)Immunohistological and flow cytometricanalysis of glycosphingolipid expression inmouse lymphoid tissues. J HistochemCytochem 48(12):1677-1690.

Bo{njak D, Maru{i} A (2000) Croatia: le-gal regulation of doctors. Lancet356(9238):1349-1350.

Glun~i} V, Maru{i} A (2000) Associationof the truncus bicaroticus, common trunk ofthe left sub-clavian and vertebral arteries,

and retro-esophageal right subclavian ar-tery. Case report. Anat Anz 182(3):281-283.

Glun~i} V, Petanjek Z, Maru{i} A, Glun~i} I(2001) High bifurcation of common carotidartery, anomalous origin of ascending pha-ryngeal artery and anomalous branchingpattern of external carotid artery. Surgical &Radiologic Anatomy 23(2):123-125.

Luki} IK, Glun~i} V, Maru{i} A (2001)Extracranial branches of the middle menin-geal artery. Clin Anat 14(4):292-294.

Luki} IK, Glun~i} V, Katavi} V, Petanjek Z,Jal{ovec D, Maru{i} A (2001) Weekly quizzesin extended-matching format as a means ofmonitoring students' progress in gross anat-omy. Ann Anat 183(6):575-579.

Zurak N (2001) Euthanasia (in Croatian).Lijec Vjesn 123(1-2):39-46.

Maru{i} A (2001) Croatia starts to involvepatients in medical decision-making. Lancet357(9272):1958.

Maru{i} A (2001) Croatian Health Minis-ter resigns after dialysis deaths. Lancet358(9291):1431.

Maru{i} A (2001) DNA lab helps identifymissing persons in Croatia and Bosnia andHerzegovina. Lancet 358(9289):1244.

Buljevac M, Grgurevi} I, Lackovi} Z,Kujund`i} M, Bani} M (2001) Duplexultrasonography in diagnosis of spigelianhernia with incarcerated jejunal loop. ActaMed Croatica 55(4-5):225-227.

[alkovi}-Petri{i} M, Mrzljak A, Lackovi} Z(2001) Usage of the Internet pharmacologyresources among European pharmacologists:a preliminary investigation. Fundamental &Clinical Pharmacology 15(1):55-60.

Dere`i} D, Zurak N, Marekovi} Z (2001)Tobacco extract used as a remedy for urinaryretention 150 years ago by the native popu-lation of the Balkans. J Ethnopharmacol76(1):133.

2002In 2002, researchers at the Croatian Institute for Brain Research (CIBR) have started to work on the CIBR's second and signif-

icantly expanded Program project entitled «Neurobiology of Cognitive Development and Cognitive Disorders». That programproject consisted of 34 individual research projects plus 2 technological projects, grouped into three main program themes,as in the previous program project:

Theme A: Neurobiology of normal and disturbed brain development: recovery and plasticity after lesion (13 projects)Theme B: Neurobiology of neurological and mental disorders with cognitive disturbances (13 projects)Theme C: Molecular pharmacology of behavior and biochemistry of neurotransmitters and second messengers (8 projects)The publications listed below are arranged in the same way (themes A, B, and C) and listed alphabetically; however, to en-

hance the browsing we included headlines denoting major research areas. We have listed exclusively original articles and re-views published in peer-reviewed journals cited in Current Contents and PubMed/Medline online databases. Names printedin bold denote group leaders or principal investigators of individual research projects (for overview of project titles and prin-cipal investigators, click here). A selected list of other publications of the CIBR's faculty (not directly related to our programproject) is provided under the heading «Other publications».

THEME A:

Developmental Neuroscience& Developmental Brain Disorders:

Bo{njak J, Vukovi}-Bobi} M, Meja-{ki-Bo{njak V (2002) Effect of war on theoccurrence of epileptic seizures in children.Epilepsy Behav 3(6):502-509.

Chan WY, Kostovi} I, Takashima S,Feldhaus C, Stoltenburg-Didinger G, VerneyC, Yew D, Ulfig N (2002) Normal and abnor-mal development of the human cerebralcortex. Neuroembryology 1:78-90.

Gong Y, Tagawa Y, Lunn MP, Laroy W,Heffer-Lauc M, Li CY, Griffin JW, SchnaarRL, Sheikh KA (2002) Localization of majorgangliosides in the PNS: implications for im-mune neuropathies. Brain 125(Pt11):2491-2506.

Groc L*, Petanjek Z*, Gustafsson B,Ben-Ari Y, Hanse E, Khazipov R (2002) In vivoblockade of neural activity alters dendriticdevelopment of neonatal CA1 pyramidalcells. European Journal of Neuroscience16(10):1931-1938. (*equally contributed)

Habek D, Habek JC, Jugovi} D, Salihagi} A(2002) Intrauterine hypoxia and sudden in-

fant death syndrome. Acta Med Croatica56(3):109-118.

Kostovi} I, Juda{ M (2002) Correlationbetween the sequential ingrowth ofafferents and transient patterns of corticallamination in preterm infants. Anat Rec267(1):1-6.

Kostovi} I, Juda{ M (2002) The role of thesubplate zone in the structural plasticity ofthe developing human cerebral cortex.Neuroembryology 1:145-153.

Kostovi} I, Juda{ M, Rado{ M, Hraba~ P(2002) Laminar organization of the humanfetal cerebrum revealed by histochemicalmarkers and magnetic resonance imaging.Cereb Cortex 12(5):536-544.

Kostovi} I, Ra{in MR, Petanjek Z, Juda{ M(2002) Morphological characteristics of thecells in the subcallosal zone (nucleusseptohippocampalis) of the human fetus.Neuroembryology 1:97-104.

Schnaar RL, Fromholt SE, Gong Y, VyasAA, Laroy W, Wayman DM, Heffer-Lauc M,Ito H, Ishida H, Kiso M, Griffin JW, Shiekh KA(2002) Immunoglobulin G-class mousemonoclonal antibodies to major braingangliosides. Analytical Biochemistry302(2):276-284.

Uylings HBM, Delalle I, Petanjek Z,Koenderink MJT (2002) Structural and

immunocytochemical differentiation of neu-rons in prenatal and postnatal humanprefrontal cortex. Neuroembryology1(4):176-186.

Vuk{i} M, Petanjek Z, Ra{in MR, Kostovi} I(2002) Perinatal growth of prefrontal layerIII pyramids in Down syndrome. PediatrNeurol 27(1):36-38.

Vyas AA, Patel HV, Fromholt SE,Heffer-Lauc M, Vyas KA, Dang J, SchachnerM, Schnaar RL (2002) Gangliosides are func-tional nerve cell ligands for myelin-associ-ated glycoprotein (MAG), an inhibitor ofnerve regeneration. Proc Natl Acad SciU.S.A. 99(12):8412-8417.

CSF Pathophysiology:

Ore{kovi} D, Klarica M, Vuki} M (2002)The formation and circulation ofcerebrospinal fluid inside the cat brain ven-tricles: a fact or an illusion? Neurosci Lett327(2):103-106.

Zmajevi} M, Klarica M, Varda R, Kudeli}N, Bulat M (2002) Elimination ofphenolsulfonphthalein from thecerebrospinal fluid via capillaries in centralnervous system in cats by active transport.Neurosci Lett 321(1-2):123-125.

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THEME B:

Psychiatry, Neurology& Molecular Neuropharmacology:

Bala`i} J, Maru{i} A (2002) Apparenthigher brain weight in suicide victims: possi-ble reasons. Psychol Rep 90(1):236-238.

Folnegovi}-[malc V, Henigsberg N, Ko-cijan-Hercigonja D, Makari} G, Mimica N,Uzun S (2002) Fifty years of psychophar-macotherapy. Lije~ Vjesn 124(11-12):378-379.

Gregurek R, Vuku{i} H, Pavi} L, Varda R,Dani} S, Gruden V, Klain E (2002) Diagnosticand therapeutic guidelines for posttrauma-tic stress disorders (in Croatian). Lijec Vjesn124(5):115-122.

He}imovi} S, Klepac N, Vla{i} J, Vojta A,Janko D, [karpa-Prpi} I, Canki-Klain N,Markovi} D, Bo`ikov J, Relja M, Paveli} K(2002) Genetic background of Huntingtondisease in Croatia: molecular analysis ofCAG, CCG, and Delta2642 (E2642del)polymorphisms. Hum Mutat 20(3):233.

Jernej B, Vladi} A, ^i~in-[ain L, Hranilovi}D, Banovi} M, Balija M, Bili} E, Su~i} Z,Vukadin S, Grgi~evi} D (2002) Platelet sero-tonin measures in migraine. Headache42(7):588-595.

Kalanj-Bognar S, Rundek T, Fura~ I,Demarin V, ^osovi} ^ (2002) Leukocytelysosomal enzymes in Alzheimer's diseaseand Down's syndrome. J Gerontol Series A –Biol Sci Med Sci 57(1):B16-B21.

Mimica N, Henigsberg N, Uzun S, LjubinT, Folnegovi} Z, Folnegovi}-[malc V (2002)Catatonic schizophrenia has a shorterpre-hospitalization interval than other typesof schizophrenia. J Neural Transm Gen Sect109(2):203-212.

[imi} G (2002) Pathological tau proteinsin argyrophilic grain disease. Lancet Neurol-ogy 1(5):276.

[tefulj J, Jakopec S, Osmak M, Jernej B(2002) Serotonin and apoptosis: studies onrat lymphocytes. Neuroimmunomodulation10(3).132-133.

Neurosurgery:

Glun~i} V, Luki} IK, Ivki} G, Hat J, Maru{i}A (2002) Accessory foramen opticum, ovale,and spinosum. Case illustration. J Neurosur-gery 96(5):965.

Paladino J, Glun~i} V, [tern-Padovan R,Vinter I, Luki} IK, Maru{i} A (2002) Cranialbase kyphosis and the surface morphologyof the anterior cranial fossa. Ann Anat184(1):21-25.

[timac A, Ivan~evi} B, Jambro{i} K (2002)Directivity pattern of neurosurgical endo-scopic ultrasonic probes. Ultrasonics40(1-8):813-818.

Neuroimaging & Radiology:

Be{enski N (2002) Traumatic injuries: im-aging of head injuries. Eur Radiol12(6):1237-1252.

Brklja~i} B, Kuzmi} AC, Dmitrovi} R, Rado{M, Vidjak V (2002) Doppler sonographic re-nal resistance index and resistance index ra-tio in children and adolescents with unilat-eral hydronephrosis. Eur Radiol12(11):2747-2751.

Glun~i} V, Luki} IK, Kopljer M,Sabljar-Matovinovi} M, Hebrang A, Maru{i}A (2002) Persistent cervical intersegmentalartery and aortic arch coarctation. SurgRadiol Anat 24(3-4):226-230.

Klapan I, [imi~i} L, Ri{avi R, Be{enski N,Pasari} K, Gortan D, Janjanin S, Pavi} D(2002) Tele-3-dimensional computer-as-sisted functional endoscopic sinus surgery:new dimension in the surgery of the noseand paranasal sinuses. Otolaryngol HeadNeck Surg 127(6):549-557.

Klapan I, [imi~i} L, Be{enski N, Bumber Z,Janjanin S, Sruk V, Mihajlovi} Z, Ri{avi R,Mladina R (2002) Application of 3D com-puter-assisted techniques to sinonasal pa-thology – case report: war wounds ofparanasal sinuses caused by metallic foreignbodies. Am J Otolaryngol 23(1):27-34.

THEME C:

Arneri} M, Traven A, Stare{ini} L, Sopta M(2002) The retinoblastoma family of pro-teins directly represses transcription inSaccharomyces cerevisiae. J Biol Chem277(11):8797-8801.

Crljen V, Volinia S, Banfi} H (2002)Hepatocyte growth factor activatesphosphoinositide 3-kinase C2 beta in renalbrush-border plasma membranes. BiochemJ 365(Pt 3):791-799.

Davidoff MS, Middendorff R, Kofuncu E,Muller D, Je`ek D, Holstein AF (2002) Leydigcells of the human testis possess astrocyteand oligodendrocyte marker molecules.Acta Histochemica 104(1):39-49.

Geber J, Parra D, Beckey NP, Korman L(2002) Optimizing drug therapy in patientswith cardiovascular disease: the impact ofpharmacist-managed pharmacotherapy clin-ics in a primary care setting. Pharmacotherapy22(6):738-747.

Ma M, Barnes G, Pulliam J, Je`ek D,Baumann RJ, Berger JR (2002) CNS angiitis ingraft vs host disease. Neurology59(12):1994-1997.

Markoti} A, Maru{i} A, Tomac J, MüthingJ (2002) Ganglioside expression in tissues ofmice lacking beta2-microglobulin. Clin ExpImmunol 128(1):27-35.

Traven A, Stare{in~i} L, Arneri} M, SoptaM (2002) The yeast protein Xtc1 functions asa direct transcriptional repressor. NucleicAcids Research 30(11):2358-2364.

Vi{nji} D, Crljen V, ]uri} J, Batini} D,Volinia S, Banfi} H (2002) The activation ofnuclear phosphoinositide 3-kinase C2beta inall-trans-retinoic acid-differentiated HL-60cells. FEBS Lett 529(2-3):268-274.

OTHER PUBLICATIONS -PATHOLOGY:

Belicza M, Leni~ek T, Glasnovi} M, Elez M,Gladi} V, Marton I, @utekovi} S, Jurlina H,Kusi} Z, Cvrtila D, Strnad M, Tomas D, ^upi} H,Kru{lin B (2002) Change in the occurrence ofbreast cancer in hospital registries(1980-2000). Lije~ Vjesn 124(11-12):347-353.

Kru{lin B, Zovak M, Doko M, Belicza M(2002) Serous oligocystic and ill-demarcatedadenoma of the pancreas. Virchow's Arch440(4):441-442.

Nola I, Kru{lin B, Muller D, Oremovi} L,Belicza M (2002) The rise in melanoma inci-dence in Croatia. Acta DermatovenerolCroat 10(1):3-7.

Novosel I, Spaji} B, Kraus O, Kru{lin B(2002) Liposarcoma of the spermatic cord:case report and review of the literature (inCroatian). Lijec Vjesn 124(5):137-139.

OTHER PUBLICATIONS – VARIA:Hebrang A, Henigsberg N, Erdelji} V,

Foro [, Turek S, Zlatar M (2002) Privatizationof the Croatian health care system: effect onindicators of health care accessibility in gen-eral medicine. Lije~ Vjesn 124(8-9):239-243.

Maru{i} A (2002) Croatia opens a na-tional centre for the prevention of smoking.Lancet 359(9310):954.

Maru{i} A (2002) Croatia restructures itsemergency medicine system. Lancet359(9320):1838.

Maru{i} A, Maru{i} M (2002) What canmedical journal editors do in war? Lancet360 (suppl):s59-60.

Maru{i} A, Luki} IK, Maru{i} M, McNameeD, Sharp D, Horton R (2002) Peer review in asmall and a big medical journal: case studyof the Croatian Medical Journal and the Lan-cet. Croat Med J 43(3):286-289.

Maru{i} A, Mi{ak A, Kljakovi}-Ga{pi} M,Maru{i} M (2002) Educatione adexcelentiam – ten years of the Croatian Med-ical Journal. Croat Med J 43(1):1-7.

Maru{i} A (2002) Peace through publichealth in southeast Europe? Lancet359(9300):54.

Vodopivec I, Vujaklija A, Hrabak M, Luki}IK, Maru{i} A, Maru{i} M (2002) Knowledgeabout and attitude towards science of firstyear medical students. Croat Med J43(1):58-62.

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2003In 2003, researchers at the Croatian Institute for brain Research (CIBR) started to work on the CIBR's collaborative research

project entitled «Development, Plasticity, and Repair of Brain After Perinatal Lesions». The collaborative project is an ex-panded continuation of the previous Theme A; however, other research groups continued to work and publish within theoverall framework of previous themes B (Neurobiology of neurological and mental disorders with cognitive disturbances)and C (Molecular pharmacology of behavior and biochemistry of neurotransmitters and second messengers).

The publications listed below are arranged in the same way as for previous years (themes A, B, and C) and listed alphabeti-cally; however, to enhance the browsing we included headlines denoting major research areas. We have listed exclusivelyoriginal articles and reviews published in peer-reviewed journals cited in Current Contents and PubMed/Medline online data-bases. Names printed in bold denote group leaders or principal investigators of individual research projects (for overview ofproject titles and principal investigators, click here). A selected list of other publications of the CIBR's faculty (not directly re-lated to our program project) is provided under the heading «Other publications».

Developmental Neuroscience &Developmental Brain Disorders:

Ammar N, Nelis E, Merlini L, Bari{i} N,Amouri R, Ceuterick C, Martin JJ,Timmerman V, Hentati F, De Jonghe P(2003) Identification of novel GDAP1 muta-tions causing autosomal recessiveCharcot-Marie-Tooth disease. NeuromusculDisord 13(9):702-728.

Bari{i} N, Logan P, Pikija S, [karpa D, BlauN (2003) R208X mutation in CLN2 gene as-sociated with reduced cerebrospinal fluidpterins in a girl with classic late infantileneuronal ceroid lipofuscinosis. Croat Med J44(4):489-493.

Burdon KP, McKay JD, Sale MM, Rus-sell-Eggitt IM, Mackey DA, Wirth MG, ElderJE, Nicoll A, Clarke MP, FitzGerald LM,Stankovich JM, Shaw MA, Sharma S,Gajovi} S, Gruss P, Ross S, Thomas P, VossAK, Thomas T, Gecz J, Craig JE (2003) Muta-tions in a novel gene, NHS, cause thepleiotropic effects of Nance-Horan syn-drome, including severe congenital cataract,dental anomalies, and mental retardation.Am J Hum Genet 73(6):1120-1130.

Dinocourt C, Petanjek Z, Freund TF,Ben-Ari Y, Esclapez M (2003) Loss ofinterneurons innervating pyramidal cell den-drites and axon initial segments in the CA1region of the hippocampus followingpylocarpine-induced seizures. J CompNeurol 459:407-425.

Duric K, [krablin S, Lesin J, Kalafati} D,Kuva~i} I, Suchanek E (2003) Second trimes-ter total human chorionic gonadotropin, al-pha-fetoprotein and unconjugated estriol inpredicting pregnancy complications otherthan fetal aneuploidy. Eur J Obstet GynecolReprod Biol 110(1):12-15.

Groc L*, Petanjek Z*, Gustafsson B,Ben-Ari Y, Khazipov R, Hanse E (2003) Com-pensatory dendritic growth of CA1 pyrami-dal cells following growth impairment inneonatal period. European Journal of Neu-roscience 18:1332-1336. (*equally contrib-uted).

Habek D, Hodek B, Herman R, Jugovi} D,^erkez-Habek J, Salihagi} A (2003) Fetalbiophysical profile and cerebro-umbillicalratio in assessment of perinatal outcome ingrowth-restricted fetuses. Fetal Diagn Ther18(1):12-16.

Juda{ M, Ra{in MR, Kru{lin B, Kostovi} K,Juki} D, Petanjek Z, Kostovi} I (2003) Den-dritic overgrowth and alterations in laminar

phenotypes of neocortical neurons in thenewborn with semilobar holoprosencephaly.Brain & Development 25:32-39.

Juda{ M, Jovanov-Milo{evi} N, Ra{in MR,Heffer-Lauc M, Kostovi} I (2003) Complexpatterns and simple architects: molecularguidance cues for developing axonal path-ways in the telencephalon. Prog Mol SubcellBiol 32:1-32.

Kolker S, Hoffmann GF, Schor DS, Feyh P,Wagner L, Jeffrey I, Pourfarzam M, Okun JG,Zschocke J, Bari} I, Bain MD, Jakobs C,Chalmers RA (2003) Glutaryl-CoAdehydrogenase deficiency: region-specificanalysis of organic acids and acylcarnitinesin post mortem brain predicts vulnerabilityof the putamen. Neuropediatrics34(5):253-260.

Kostovi} I, ed. (2003) Guidance Cues inthe Developing Brain (Progress in Molecularand Subcellular Biology vol. 32). Berlin:Springer-Verlag, 145pp.

Lesin J, [krablin S, Duric K, Suchanek E,Mu`ini} D, Kalafati} D, Kuva~i} I, Zlopa{a G,Plavec A (2003) Screening for Down syn-drome using triple marker testing in the sec-ond trimester of pregnancy. Lije~ Vjesn125(3-4):55-60.

Muro AF, Chauhan AK, Gajovi} S,Iaconcig A, Porro F, Stanta G, Baralle FE(2003) Regulated splicing of the fibronectinEDA exon is essential for proper skin woundhealing and normal lifespan. J Cell Biol162(1):149-160.

Muth A, Mosandl A, Wanders RJ,Nowaczyk MJ, Bari} I, Bohles H, Sewell AC(2003) Stereoselective analysis of2-hydroxysebacic acid in urine of patientswith Zellweger syndrome and of prematureinfants fed with medium-chain triglycerides.J Inherit Metab Dis 26(6):583-592.

[imi} G, Diana A, Hof PR (2003)Phosphorylation pattern of tau associatedwith distinct changes of the growth conecytoskeleton. Prog Mol Subcell Biol32:33-48.

Zschocke J, Preusse A, Sarnavka V, Fumi}K, Marde{i} D, Hoffmann GF, Bari} I (2003)The molecular basis of phenylalanine hy-droxylase deficiency in Croatia. Hum Mutat21(4):399.

CSF Pathophysiology:

Ore{kovi} D, Klarica M, Vuki} M, Ma-rakovi} J (2003) Evaluation of ventri-culo-cisternal perfusion model as a method

to study cerebrospinal fluid formation.Croat Med J 44(2):161-164.

Psychiatry, Neurology,Neuropathology & MolecularNeuropharmacology:

Hranilovi} D, [tefulj J, Fura~ I, Kubat M,Balija M, Jernej B (2003) Serotonin trans-porter gene promoter (5-HTTLPR) and intron2 (VNTR) polymorphisms in Croatian suicidevictims. Biol Psychiatry 54(9):884-889.

Juri} G, Jaki}-Razumovi} J, Rotim K,@arkovi} K (2003) Extranodal sinus hi-stiocytosis (Rosai-Dorfman disease) of thebrain parenchyma. Acta Neurochir (Wien)145(2):145-149.

Pavi} L, Gregurek R, Petrovi} R, Petrovi}D, Varda R, Vuku{i} H, Crnkovi}-Markovi} S(2003) Alterations in brain activation inposttraumatic stress disorder patients withsevere hyperarousal symptoms and impul-sive aggressiveness. Eur Arch Psychiatry ClinNeurosci 253(2):80-83.

Pe}ina-[laus N (2003) Tumor suppressorgene E-cadherin and its role in normal andmalignant cells. Cancer Cell Int. 3(1):17.

[alkovi}-Petri{i} M, Lackovi} Z (2003)Intracerebroventricular administration ofbetacytotoxics alters expression of brainmonoamine transporter genes. J NeuralTransm 110(1):15-29.

Vidovi} V, Henigsberg N, Jure{a V (2003)Anxiety and defense styles in eating disor-ders. Coll Anthropol 27 (suppl 1):125-134.

@arkovi} K (2003) 4-hydroxynonenal andneurodegenerative diseases. Mol AspectsMed 24(4-5):293-303.

Neurosurgery:

Mahovi}-Laku{i} D, Petravi} D, Zurak N,Paladino J, Juri} G (2003) Isolated cervicalspinal cord hemangioblastoma – case re-port. Lije~ Vjesn 125(5-6):129-131.

THEME C:

Fon Tacer K, Kalanj-Bognar S, WatermanMR, Rozman D (2003) Lanosterol metabo-lism and sterol regulatory element bindingprotein (SREBP) expression in male germ cellmaturation. J Steroid Biochem Mol Biol85(2-5):429-438.

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Trkulja V, @iv~ec Z, ]uk M, Lackovi} Z(2003) Use of psychoactive substancesamong Zagreb University medical students:follow-up study. Croat Med J 44(1):50-58.

Vi{nji} D, ]uri} J, Crljen V, Batini} D, VoliniaS, Banfi} H (2003) Nuclear phosphoinositide3-kinase C2beta activation during G2/Mphase of the cell cycle in HL-60 cells. BiochimBiophys Acta 1631(1):61-71.

OTHER PUBLICATIONS –PATHOLOGY:

Heller A, Bre~evi} L, Glaser M, Lon~arevi}I, Gebhart E, Claussen U, Liehr T (2003)Trisomy 8 as the sole chromosomal aberra-tion in myelocytic malignancies: a compre-hensive molecular cytogenetic analysis re-veals no cryptic aberrations. Cancer GenetCytogenet 146(1):81-83.

Kru{lin B, Tomas D, Rogatsch H, NovoselI, ^upi} H, Belicza M, Kraus O, Mikuz G

(2003) Periacinar retraction clefting in theprostatic needle core biopsies: an importantdiagnostic criterion or a simple artifact?Virchows Arch 443(4):524-527.

Kru{lin B, Tur~i} M, ^upi} H, Novosel I,Relji} A, Ru`i} B, Belicza M (2003) Impor-tance of determination of various histologiccomponents in testicular germ cell tumors.Lije~ Vjesn 125(9-10):242-245.

Paveli} K, Kolak T, Kapitanovi} S,Rado{evi} S, Spaventi S, Kru{lin B, Paveli} J(2003) Gastric cancer: the role of insulin-likegrowth factor 2 (IGF 2) and its receptors (IGF1R and M6-P/IGF 2R). J Pathol201(3):430-438.

Pe}ina-[laus N, Milavec-Pureti} V, KubatM, Fura~ I, Karija M, Fischer-Zigmund M,Lipozen~i} J (2003) Clinical case of acralhemorrhagic Darier's disease is not causedby mutations in exon 15 of the ATP2A2gene. Coll Anthropol 27(1):125-133.

Stanimirovi} A, ^upi} H, Bo{njak B,Kru{lin B, Belicza M (2003) Expression ofp53, bcl-2 and growth hormone receptor inactinic keratosis, hypertrophic type. ArchDermatol Res 295(3):102-108.

@arkovi} N, @arkovi} K, Kralj M, Borovi} S,Sabolovi} S, Bla`i MP, Cipak A, Paveli} K(2003) Anticancer and antioxidative effectsof micronized zeolite clinoptilolite.Anticancer Res 23(2B):1589-1595.

OTHER PUBLICATIONS – VARIA:Gamulin S (2003) Impact of molecular

medicine on pathophysiology, medical prac-tice, and medical education. Croat Med J44(4):374-385.

Hebrang A, Henigsberg N, Erdelji} V, Foro[, Vidjak V, Grga A, Ma~ek T (2003) Privat-ization in the health care system of Croatia:effects on general practice accessibility.Health Policy Plan 18(4):421-428.

2004.

THEME A:Developmental Neuroscience& Developmental Brain Disorders(COLLABORATIVE PROGRAME):

1. Crljen, V; Vi{nji}, D; Banfi}, H. Pres-ence of different phospholipase Cisoforms in the nucleus and their acti-vation during compensatory livergrowth. // FEBS Letters. 571 (2004) , 1;35-42.

2. Trkulja, V; Crljen-Manestar, V; Banfi},H; Lackovi}, Z. Involvement of the pe-ripheral cholinergic muscarinic systemin the compensatory ovarian hypertro-phy in the rat. // Experimental Biologyand Medicine. 229 (2004) , 8; 793-805.

3. Bordukalo-Nik{i}, T; ^i~in-[ain, L; Jer-nej, B. Expression of brain and plateletserotonin transporters in sublines ofrats with constitutionally altered sero-tonin homeostasis. // Neuroscience Let-ters. 369 (2004) , 1; 44-49.

4. Hranilovi}, D; [tefulj, J; Schwab, S;Borrmann-Hassenbach, M; Albus, M;Jernej, B; Wildenauer, D. Serotonintransporter promoter and intron 2polymorphisms: relationship betweenallelic variants and gene expression. //Biological Psychiatry. 55 (2004) , 11;1090-1094.

5. Abrami}, M; [imaga, [; Osmak, M; ^i-~in-[ain, L; Vukeli}, B; Vlahovi~ek, K;Dolov~ak, Lj. Highly reactive cysteineresidues are part of the substrate bind-ing site of mammalian dipeptidyl pep-tidases III. // The International Journal ofBiochemistry & Cell Biology. 36 (2004) ;434-446.

6. [imi}, G; Bexheti, S; Kelovi}, Z; Kos, M;Grbi}, K; Hof, PR.; Kostovi}, I. Hemi-spheric asymmetry, modular variabil-ity and age-related changes in the hu-man entorhinal cortex. // Neurosci-ence. 130 (2005) , 4; 911-925.

7. Kostovi}, I; Jovanov-Milo{evi}, N;Meja{ki-Bo{njak, V; Kostovi}, M;Rado{, M; Petanjek, Z; Gojmerac, T;Juda{, M. Development and structuralplasticity of the human brain. // Gynae-cology and Perinatology. 13 (2004) ,Suppl 2; 35-40

8. Bari} I, Fumi} K, Glenn B, ]uk M,Schulze A, Finkelstein JD, James SJ,Meja{ki-Bo{njak V, Pa`anin L, PogribnyIP, Rado{ M, Sarnavka V, [~uka-nec-[poljar M, Allen RH, Stabler S,Uzelac L, Vugrek O, Wagner C, Zeisel S,Mudd SH (2004) S-adenosylhomo-cysteine hydrolase deficiency in a hu-man: a genetic disorder of methioninemetabolism. Proc Natl Acad Sci USA101(12):4234-4239.

9. Belovari T, Stevi} N, Gajovi} S,Kostovi}-Kne`evi} Lj (2004) Differen-tiation and develomental potential ofrat post-implantation embryo with-out extra-embryonic membranes cul-tured in vitro or grafted in vivo. AnatHistol Embryol 33(2):90-95.

10. Canki-Klain N, Mili} A, Kova~ B, TrlajaA, Grgi~evi} D, Zurak N, Fardeau M,Leturcq F, Kaplan JC, Urtizberea JA,Politano L, Piluso G, Feingold J (2004)Prevalence of the 550delA mutationin calpainopathy (LGMD 2A) inCroatia. Am J Med Genet125A(2):152-156.

11. [krablin S, Banovi} VV, Kuva~i} I(2004) Morbid maternal obesity andpregnancy. Int J Gynaecol Obstet85(1):40-41.

12. Walter MC, Petersen JA, Stucka R,Fuscher D, Schroder R, Vorgerd M,Schroers A, Schreiber H, HanemannCO, Knirsch U, Rosenbohm A,Huebner A, Bari{i} N, Horvath R,Komoly S, Reillich P, Muller-Felber W,Pongratz D, Muller JS, Auerswald EA,Lochmuller H (2004) FKRP (826C>A)

frequently causes limb-girdle muscu-lar dystrophy in German patients. JMed Genet 41(4):e50.

13. Bindila, L; Froesch, M; Lion, N;Vukeli}, @; Rossier, J; Girault, HH; Pe-ter-Katalini}, J; Zamfir, A. Thin ChipMicrosprayer System Coupled to Fou-rier Transform Ion Cyclotron Reso-nance Mass Spectrometry forGlycopeptide Screening. // RapidCommunications in Mass Spectrome-try. 18 (2004) , 23; 2913-2920.

14. Zamfir, A; Vukeli}, @; Bindila, L; Pe-ter-Katalini}, J; Almeida, R; Sterling, A;Allen, M. Fully-automated chip-basednanoelectrospray tandem mass spec-trometry of gangliosides from humancerebellum. // Journal of The AmericanSociety for Mass Spectrometry. 15(2004) , 11; 1649-1657.

15. @untar, I; Kalanj-Bognar, S; Topi}, E;Petlevski, R; [tefanovi}, M; Demarin,V. The glutathione S-transferasepolymorphisms in a control popula-tion and in Alzheimer's disease pa-tients. // Clinical chemistry and labora-tory medicine. 42 (2004) , 3; 334-339.

16. Sun, J; Shaper, NL.; Itonori, S; He-ffer-Lauc, M; Sheikh, KA.; Schnaar, RL.Myelin-associated glycoprotein(siglec-4) expression is progressivelyand selectively decreased in the brainsof mice lacking complex gangliosides.//Glycobiology. (2004) ; 1-24.

17. Habek, D; Jugovic, D; Hodek, B;Herman, R; Maticevic, A; Habek ^,Jasna; P, Zoran; Salihagic, A. Fetalbiophysical profile and cerebro-umbil-ical ratio in assessment of brain dam-age in growth restricted fetuses. // Eu-ropean Journal of Obstetrics, Gynecol-ogy and Reproductive Biology. 114(2004) , 1; 29-34.

18. Kurjak, A; Stanojevi}, M; Andonotopo,W; Salihagi}-Kadi}, A; Carrera, JM;

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Azumendi, G. Behavioral pattern con-tinuity from prenatal to postnatallife--a study by four-dimensional (4D)ultrasonography. // Journal of PerinatalMedicine. 32 (2004) ; 346-53

19. [erman, Lj; [erman, A; Lauc, G; Mili},A; Latin, V; Aleksandrova, A; [erman,D. Comparison of Glycosylation Pat-terns of Placental Proteins BetweenNormal Pregnancy and Missed Abor-tion. // Collegium Antropologicum. 28(2004) , 1; 301-308.

THEME B:Psychiatry, Neurology & Molecu-lar Neuropharmacology:

1. Dossenbach MR, Folnegovi}-[malc V,Hotujac L, Ugle{i} B, Tollefson GD,Grundy SL, Friedel P, Jakovljevi} MM(2004) Olanzapine HGCH Study Group.Double-blind, randomized comparisonof olanzapine versus fluphenazine inthe long-term treatment of schizo-phrenia. Prog NeuropsychopharmacolBiol Psychiatry 28(2):311-318.

2. Folnegovi}-[malc V, Juki} V, Ko-zumplik O, Mimica N, Uzun S (2004)Olanzapine use in a patient withschizophrenia and the risk of diabe-tes. Eur Psychiatry 19(1):62-64.

3. Zuntar I, Kalanj-Bognar S, Topi} E,Petlevski R, Stefanovi} M, Demarin V(2004) The glutathione S-transferasepolymorphisms in a control popula-tion and in Alzheimer's disease pa-tients. Clin Chem Lab Med42(3):334-339.

4. Jost WH, Heinen F, Marziniak M, ReljaM, Schulte-Mattler W, Schmidt U,Vollmer-Haase J (2004) Botulinumtoxin in tension-type headache. JNeurol 251 (Suppl1):33-35.

5. Relja M, Telarovi} S (2004) Botulinumtoxin in tension-type headache. JNeurol 251 (Suppl1):12-14.

6. Fili}, V; Vladi}, A; [tefulj, J; ^i~in-[ain,L; Balija, M; Su~i}, Z; Jernej, B.Monoamine Oxidases A and B GenePolymorphisms in Migraine Patients. //Journal of the Neurological Sciences.(2004).

7. Jernej, B; [tefulj, J; Hranilovi}, D;Balija, M; [kavi}, J; Kubat, M. Intronicpolymorphism of tryptophan hydroxy-lase and serotonin transporter: indica-tion for combined effect in predisposi-tion to suicide. // Journal of NeuralTransmission. 111 (2004) , 6; 733-738.

8. [tefulj, J; Büttner, A; Kubat, M; Zill, P;Balija, M; Eisenmenger, W; Bondy, B;Jernej, B. 5HT-2C receptor polymor-phism in suicide victims: associationstudies in German and Slavic popula-tions. // European Archives of Psychia-try and Clinical Neuroscience. 254(2004) , 4; 224-227 (~lanak, znanstvenirad).

9. [tefulj, J; Büttner, A; [kavi}, J; Zill, P;Balija, Ma; Eisenmenger, W; Bondy, B;Jernej, B. Serotonin 1B (5HT-1B) re-ceptor polymorphism (G861C) in sui-cide victims: association studies inGerman and Slavic population. //American Journal of Medical Genetics.127B (2004) , 1; 48-50 (~lanak,znanstveni rad

10. [tefulj, J; Kubat, M; Balija, M; [kavi},J; Jernej, B. Variability of thetryptophan hydroxylase gene : studyin victims of violent suicide. // Psychia-try research. (2004).

THEME C:

1. Cotman, M; Je`ek, D; Fon Tacer K;Frange`, R; Rozman, D. A functional

cytochrome P450 lanosterol 14� ; ;-demethylase CYP51 enzyme in theacrosome: transport through the Golgiand synthesis of meiosis-activating ster-ols.. // Endocrinology. 145 (2004) , 3;1419-1426.

2. Je`ek, D; Kne`evi}, N; Kalanj-Bognar, S;Vukeli}, @; Krhen, I. From testicular bi-opsy to human embryo. // Verhleiungender Deutsche Gesellschaft furPathologie. 88 (2004) ; 1-8.

3. Mari} S, Buli}-Jaku{ F, Je`ek D,Juri}-Leki} G, Kos M, Vlahovi} M (2004)Expression of the proliferating cell nu-clear antigen and protein products oftumour suppressor genes in the humanfoetal testis. Andrologia 36(1):24-30.

4. Cotman M, Je`ek D, Fon Tacer K,Frangez R, Rozman D (2004) A functionalcytochrome P450 lanosterol 14 al-pha-demethylase CYP51 enzyme in theacrosome: transport through the Golgiand synthesis of meiosis-activating ster-ols. Endocrinology 145(3):1419-1426.

OTHER PUBLICATIONS –PATHOLOGY:

1. Pe}ina-[laus N, Gall-Tro{elj K, [laus M,Radi} K, Niku{eva-Marti} T, Paveli} K(2004) Genetic changes of theE-cadherin and APC tumour suppressorgenes in clear cell renal cell carcinoma.Pathology 36(2):145-151.

2. Stanimirovi} A, ^upi} H, Bo{njak B,Tomas D, Bali~evi} D, Kru{lin B, BeliczaM (2004) Expression of p53, bcl-2 andgrowth hormone receptor in atrophictype of actinic keratosis. J Dermatol Sci34(1):49-53.

OTHER PUBLICATIONS – VARIA:1.Maru{i} A, Markoti} A, Kova~i} N,

Muthing J (2004) Expression ofglycosphingolipids in lymph nodes ofmice lacking TNF receptor 1: biochemicaland flow cytometry analysis. CarbohydrRes 339(1):77-86.

Joint Publications of CIBR and Diagnostic Center "Neuron"Only publications not contained in the main list

1. Jelovac, Nikola; Sikiri}, Predrag; Ru~man,Rudolf; Petek, Marijan; Marovi}, Anton;Perovi}, Darko; Seiwerth, Sven; Mi{e,Stjepan; Turkovi}, Branko; Dodig, Goran;Mikli}, Pavle; Buljat, Gojko; Prka}in, Ing-rid. Pentadecapeptide BPC 157 attenu-ates disturbances induced by neuro-leptics: the effect on catalepsy and gas-tric ulcers in mice and rats.. // EuropeanJournal of Pharmacology. 379 (1999.) ,1; 19-31.

2. Sikiri}, Predrag; Mazul, Branka; Sei-werth, Sven; Grabarevi}, @eljko;Ru~man, Rudolf; Petek, Marijan; Jagi},Vjekoslav; Turkovi}, Branko; Rotkvi},Ivica; Mi{e, Stjepan; Zori~i}, Ivan;Jurina, Ljubica; Konjevoda, Pa{ko;Han`eva~ki, Miroslav; Gjura{in, Miro-

slav; [eparovi}, Jadranka; Ljubanovi},Danica; Artukovi}, Branka; Bratuli},Mirna; Ti{ljar, Marina; Mikli}, Pavle;Sumajstor~i}, Jagoda. Pentadecapep-tide BPC 157 interactions withadrenergic and dopaminergic systemsin mucosal protection in stress. // Di-gestive Diseases and Sciences. 42(1997) , 3; 661-71.

3. Sikiri}, Predrag; Miku{, Darko;Seiwerth, Sven; Grabarevi}, @eljko;Ru~man, Rudolf; Petek, Marijan; Jagi},Vjekoslav; Turkovi}, Branko; Rotkvi},Ivica; Mi{e, Stjepan; Zori~i}, Ivan; Peri},J.; Konjevoda, Pa{ko; Perovi}, Darko;Jurina, Ljubica; Han`eva~ki, Miroslav;[eparovi}, Jadranka; Gjura{in, Miro-slav; Jadrijevi}, Stipe; Jelovac, Nikola;

Mikli}, Pavle; Buljat, Gojko; Marovi},Anton. Pentadecapeptide BPC 157,cimetidine, ranitidine, bromocriptine,and atropine effect in cysteamine le-sions in totally gastrectromized rats: amodel for cytoprotective studies. // Di-gestive Diseases and Sciences. 42(1997) , 5; 1029-37.

4. ^ubeli}, Sndra; Meja{ki-Bo{njak,Vlatka; Bori}, Igor; Rogulj, Kata. . //Paediatria Croatica. 47 (2003) ; 87-90.

5. Meja{ki-Bo{njak, Vlatka; Luji}, Lucija;Bo{njak, Jelena; Jaku{i}, Nenad; Bori},Igor. . // Brain & Development. 26(2004); S21.

announcement

52 www.mef.hr

announcement mef.hr

�

SECOND FENS/IBRO INTERNATIONAL SUMMER SCHOOL

''Development and Plasticityof the Human Cerebral Cortex''Zadar – Zagreb, CroatiaSeptember 25 – October 04, 2005

The course is intendedfor advanced Ph.D. stu-dents or post-docs in neu-roscience and relatedfields, below the age of 35years. Young scientistsfrom both Western Europeand IBRO-CEERC Region, aswell as from the other IBROregions, are encouraged toapply. A total of 26 stu-dents will be accepted.

The School will havetwo parts, with the firstpart (7 days, invited lec-tures) held in Zadar (Borik),Croatia and the secondpart (two days practical tu-torials plus one morningfor evaluations) held in lab-oratories of the CroatianInstitute for Brain Research(CIBR) in Zagreb, Croatia.

Topics include: neurogenetic eventsin the human cerebral cortex – prolifer-ation, migration and cell lineages;synaptogenesis, development of den-drites and formation of thalamocor-tical, corticocortical and monoaminer-gic connections; genetic and molecularmechanisms of regionalization and cor-tical areal specification; molecular pat-terning of cortical neurons; neuro-physiology of immature human cortex;characteristics of early cortical net-work; development and plasticity ofhippocampal circuitry and signalingmolecules; development of workingmemory and executive functions innon-human primates and normal anddyslexic children; neuroimaging of cor-tical development; neuronal imaging ofthe human fetal brain; DTI mapping ofhuman brain connectivity; vulnerabilityin cortical development; animal modelsof developmental pathologies; plastic-ity, recovery, repair of cortex andneurodevelopmental outcome afterperinatal damage; neuroprotection inearly life; generic vs. species-specificfeatures of human neocortical evolu-tion.

Practical courses (conducted byCIBR's faculty) include: MRI and otherneuroimaging methods; Neurolucida &Stereoinvestigator systems; single cellelectrophysiological recording; multi-ple immunocytochemical labeling tech-niques; in situ hybridization; electronmicroscopy; confocal microscopy.

Outlines of teaching program andpractical course are posted on:http://www.hiim.hr/english/index.html

Teaching materials and reference topublications that relate to the maintopics of the School program will beprovided to the students before theopening of the School.

Faculty include: Yehezkel Ben-Ari,Nenad Bogdanovic, Thomas Deller,Philippe Evrard, Monique Esclapez,Laurence Garey, Giorgio M. Innocenti,Milos Judas, Kai Kaila, Bozena Ka-minska, Henry Kennedy, Torkel Kling-berg, Ivica Kostovic, O.A. Krishtal, Kre-simir Krnjevic, Heiko Luhmann, PhilippeMaeder, Pamela Moses, Robert Nitsch,Ante L. Padjen, Daniela Prayer, LuisPuelles, Pasko Rakic, Mary A. Ru-therford, Nenad Sestan, Joan Stiles,Harry B.M. Uylings, Allesandro Vercelliand Catherine Verney.

Applications shouldcontain: a curriculum vi-tae, a list of publications, arecommendation of thementor/supervisor, and aone-page abstract of a 10min talk or poster presen-tation that applicant is ex-pected to present duringthe course (for better re-sults please follow guide-lines for their preparationsavailable on:http://www.ibro.org/Pub_Main_Dis-play.asp?Main_ID=163)

Faculty Committee willevaluate the applicationsand the list of participantswill be announced duringthe 3rd week of May 2005.

Applications should be sentto the main organizer:

Prof. Ivica Kostovic, Croatian Institutefor Brain Research, School of Medicine,University of Zagreb, Salata 12, 10000Zagreb, CROATIA

E-mail: schoolºhiim.hr orikostovºhiim.hr

DEADLINE FOR APPLICATIONIS MAY 1, 2005

Organizers of the Summer School:

Main organizers: Ivica Kostovic, MilosJudas, Marijan Klarica, Goran Simic,Zdravko Petanjek and Srecko Gajovic.

Local organizing committee: NatasaJovanov–Milosevic, Zeljka Krsnik, Kristi-na Grbic, Dinko Mitrecic and SvjetlanaBognar-Kalanj.

Practical course organizers: ZdravkoPetanjek, Ileana Hanganu, Roko MladenRasin, Milan Rados and Mario Vuksic.

The costs of registration, accommo-dation and meals will be covered for allstudents.

The support for the School will beprovided by FENS, IBRO and CroatianMinistry of Science.

mef.hrZAGREB UNIVERSITY SCHOOL OF MEDICINE OFFICIAL JOURNAL / www.mef.hr

Volume 24, No 1

ISSN 1332-960X

• How the Institute was Built . . . . . . . . . . . . . . . . . . . . . . . . . . 3

• Organizing Centre of Excellence . . . . . . . . . . . . . . . . . . . . . 8

• Progress Report on Activitiesof the Institute. . . . . . . . . . . . . . . . . 10

• Research Units . . . . . . . . . . . . . . . . . 19

• Institute Publications for the period 1997 - 2004. . . . . . . . . . . . . . . . . . . . . . 43

Fif

teen years

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STITUTE FOR

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Special Issue

Special Issue

Since its outset in 1917 theSchool of Medicine at the Univer-sity of Zageb has encouragedequal development of the threebasic constituents of medical sci-ence: clinical medicine, essentialfor restoring health, basic medicalsciences, essential for the develop-ment of medicine as a science, andpublic health, essential for thehealth of the community.

Since its founding, both facultymembers and students of theSchool have been and will contin-ue to be dedicated to excellence ineducation, research and service tothe nation.

The Zagreb School of Medicinehas a distinguished tradition in thefield of neurology as well as sever-al internationally recognizedresearch groups with long-stand-ing research experience in the fieldof neuroscience. Therefore in theearly 90's brain research wasselected as one of the research anddevelopmental priorities.

A Word fromthe Dean

MARCH 2005

phone: +385 1 4564567; fax: +385 1 7897896; e-mail: hiim@hiim.hr; www.hiim.hr

In 1990 the Ministry of Scienceof the Republic of Croatia accept-ed the initiative of the ZagrebSchool of Medicine and supportedthe establishment of the BasicSciences Building and the CroatianInstitute for Brain Research(C.I.B.R.).

In this way, Croatia joined theinternational efforts in the Decadeof the Brain, clearly recognizingthe need for research on the neu-robiological basis and mental dis-orders, as well as the need for amore intensive collaboration withinternational institutions.

The University of Zagreb Schoolof Medicine is also a leading insti-tution in medical education inCroatia. For medical education it isimportant that the major goal ofthe C.I.B.R. is to provide a strongscientific background for graduate(MD), doctoral (PhD) and continu-ing education.

The courses at the School arebased on a well-balanced curricu-lum where students acquire specif-ic skills and knowledge necessaryfor health care. Recently a newPhD program in Biomedicine and

Professor Nada »ikeπ, M.D., Ph.D., Dean

NAME: Croatian Institute for Brain Research

ADDRESS: ©alata 12, 10000 Zagreb, Croatia

USEFULL SPACE: 5500 m2

NUMBER OF REASERCHERS HOLDING Ph. D. DEGREE: 50

NUMBER OF LABORATORIES: 25

PROJECTS: 59

Professor Ivica KostoviÊ, M.D. Ph.D.director and founder

of the Institute

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