using the fst to correlate depressive-like behavior and estrogen levels in three strains of mice

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Using the FST to Correlate Depressive- Like Behavior and Estrogen Levels in Three Strains of Mice Kunwal Nasrullah Columbia University, College of Physicians and Surgeons D. Toran-Allerand M.D., Sc.D. Imam Nethrapalli, PhD

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Page 1: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Kunwal Nasrullah

Columbia University, College of Physicians and Surgeons

D. Toran-Allerand M.D., Sc.D.

Imam Nethrapalli, PhD

Page 2: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Key TermsDepression-“symptoms meeting established clinical threshold criteria

for depression as measured by validated questionnaires or standardized psychiatric interviews”¹ vs. depressive-like behavior

Forced Swimming Test (FST)-a behavior test that serves as a rodent model for depressive-like symptoms in humans.

Estrogens- 17β-estradiol vs. 17α-estradiol

Mice strains: BALB/c, 129/SvEv, and c57BL/6J

Intact vs. Ovariectomized (OVX) vs. Adrenalectomized (ADRX)

For All Lab
Rats or mice are placed in cylinders filled with water at 25ºC and their immobility (i.e. floating) is the parameter for measuring depression. Porsolt et al., 1978 R.D. Porsolt, G. Anton, N. Blavet and M. Jalfre, Behavioural despair in rats: a new model sensitive to antidepressant treatments, Eur. J. Pharmacol. 47 (1978), pp. 379–391.
For All Lab
no set definition of depression besides a rating symptom; depression is a syndrome; this def. found in articles dealing w/ identifying depression-Questionnaires:Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS)Frasure-Smith N, Lesperance F, Talajic M, et al. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270:1819–25.Depressive-like symptoms: symptoms that mimic human depression, such as inactivity and lack of curiosity
For All Lab
17beta: effects on sexual reproduction (prevents male gametes from apoptosis), neuroprotective, oncogene (breast and uterine cancer), etc17alpha: thought to be less active HOWEVER -neuroprotective, more active at 1 picomole than 17beta in cell mitogenesisactive in MAPK/ERK1 and 2 signalling INVOLVED IN MITOSIS; growth...shown to be produced locally in the brain by Toran-Allerand, et alToran-Allerand CD, Tinnikov AA, Singh RJ, Nethrapalli IS 2005 17alpha-estradiol:a brain-active estrogen? Endocrinology 146:3843–3850.
Page 3: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

What I do…

I am a double-blind scorer of mice FST conducted by my co-mentor, Imam Nethrapalli. Our ongoing project is to test the hypothesis that 17α-estradiol is produced locally in the brain and that it has antidepressant activities in mice.

Page 4: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

What I see…

http://www.biobserve.com/products/fst/acquisition_movie.html

Computer Image of FST

http://62.193.209.148/en/content.php?content.66

Page 5: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Things that I look for…

During an FST scoring, three actions can be observed:

swimmingclimbing/scratching along the sides of the container floating/immobility: no active movement

HINT: The surface of the water is a good indicator of movement or immobility.

Page 6: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Possible ResultsMy results can help to validate

previous findings of my mentor.

It is also possible that my results will negate the findings of my mentor.

In either case, it is necessary to certify the antidepressant effects of 17α-estradiol in mice.

These results will be used in a paper.

Page 7: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Future PlansI will continue to score the FST

relevant to the study and learn lab techniques related to these behavior studies.

We will add results of an Open Field Test (a 3-by-3 feet square made of melamine which allows researchers to gauge the anxiety of mice and rats) to the results of the FST to support the lab’s work.

http://www.biochemj.org/bj/389/0593/bj3890593f01.gif

Open Field Test

For All Lab
http://www.psychiatry.uc.edu/BehaviorCore/HTML/openfield.html
Page 8: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

References(2007). Bioserve: solutions for your science. Retrieved August 2, 2007 from

http://www.biobserve.com/products/fst/acquisition_movie.html.

(2006). Cheshire wildlife trust. Retrieved August 2, 2007 from http://www.wildlifetrust.org.uk/cheshire/IMAGES/watch_harvest_mice.jpg.

¹ Frasure-Smith N, Lesperance F, Talajic M, et al. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270:1819–25.

Porsolt et al., 1978 R.D. Porsolt, G. Anton, N. Blavet and M. Jalfre, Behavioural despair in rats: a new model sensitive to antidepressant treatments, European Journal of Pharmacology. 47 (1978), pp. 379–391.

Toran-Allerand CD, Tinnikov AA, Singh RJ, Nethrapalli IS. 2005. 17alpha-estradiol: a brain-active estrogen? Endocrinology, 146:3843–3850.

van Meer, P., & Raber, J. (2005). Mouse behavioral analysis in systems biology. Biochemical journal, 389. Retrieved August 1, 2007, from http://www.biochemj.org/bj/389/0593/bj3890593.htm.

Villalba, Shannon. (2005). The behavior core. Retrieved August 1, 2007 from http://www.psychiatry.uc.edu/BehaviorCore/HTML/openfield.html.

Page 9: Using the FST to Correlate Depressive-Like Behavior and Estrogen Levels in Three Strains of Mice

Acknowledgments

Dr. Sat

HCS

HCS staff

Dr. Toran-Allerand

Dr. Imam Nethrapalli

Caitlin

Columbia University, College of Physicians and Surgeons

MSKCC

And you!