Introduction to Neuroglia: Definition, Classification, Evolution

1 Definition of neuroglia

There is no clear definition for neuroglia: most of the existing ones depict neuroglia as a supportive element of the nervous systemFor example: “The supportive tissue of the nervous system”http://www.thefreedictionary.com/“sustentacular tissue that surrounds and supports neurons in the central nervous system”Web definitions from google.com“supporting structure of nervous tissue”www.aimsusa.org/UsefulDefinitions.htm

Neuroglia (always plural) represent all cells in the brain which are not neurones and which are electrically non-excitable

We may define neuroglia as a heterogeneous population ofcells of neural and non-neural origin responsible for brainhomeostasis (all neuroglia), myelination (oligodendrocytes)and defence (astrocytes and microglia).

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Diversity of Neuroglia

etc.

Verkhratsky & Butt (2013): Physiology and Pathophysiology of Neuroglia, Wiley, 560 pp.

3 Neuronal-glial network

Kettenmann, Kirchhoff & Verkhratsky A. (2013). Neuron 77, 10-18.

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Glia to neurone ratio

Neurones/Non-neuronal cells numbers were determined by isotopic fractionation,which calculates total number of nuclei and total number of NeuN-positive cells that are considered to be neurones.

Azevedo, Carvalho, Grinberg, Farfel, Ferretti, Leite, Jacob Filho, Lent & Herculano-Houzel (2009): J Comp Neurol 513, 532-541.

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Glia-neuronal ratio in various structures of the human brain:

Cortical grey matter 1.65 : 1

White mater: ~ infinity: 0

Thalamus 17 : 1

Brainstem ~ 10 : 1

Cerebellum 0.1 – 0.25 : 1

Glia to neurone ratio 6

Evolution of neuroglia

7 Evolution of glia

Verkhratsky & Butt (2013): Physiology and Pathophysiology of Neuroglia, Wiley

8

Phylogenetic advance of glia

Oberheim, Wang, Goldman, Nedergaard (2006): Trends Neurosci 29, 547-553Verkhratsky & Butt (2007): Glial Neurobiology, A Textbook; Wiley & Sons

9 Primate-specific glial cells

Oberheim, Wang, Goldman, Nedergaard (2006): Trends Neurosci 29, 547-553.

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Evolution of glial function

11Functions of invertebrate glia: Ancestral astrocytes

Metabolic support of neurones (Nematodes)

Regulation of development (Nematodes)

Control of extracellular ion homeostasis (Nematodes)

Isolation/separation of nervous circuitsCompartmentalisation of the nervous system (Annelida)

Increase of axonal conduction velocitythrough formation of multilayered glial sheath around axons (Annelida and some Arthropoda – prawns)

Formation of blood-brain barrier (Arthropoda)

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Neuroglia in Caenorhabditis elegans

C. elegans has 302 neurons and 56 glial cells. Glial cell types:50 cells cover dendrites of sensory neurons; 4 of these 50 (CEP sheath glia) envelop the nerve ring and send processes to some synaptic sites in the brain. 6 cells (GLR glia) form gap junctions to both muscle cells and motor neurons.

Artificial ablation of glia in C. elegans does not kill neurones but greatly affects their development (neuronal assembly and neurite morphogenesis) and function

Bacaj, T, Tevlin, M, Lu, Y & Shaham, S, (2008): Science 322, 744-747.

C. elegans glia may also have sensory functions(from Shai Shaham laboratory webpagehttp://shahamlab.rockefeller.edu/research.php)

Calcium signalling in C.elegans glia is controlled mainly by voltage-gated Ca channels (Vlad Parpura, personal communication.

The ancestral glia retains some neuronal features

Verkhratsky & Butt (2013): Physiology and Pathophysiology of Neuroglia, Wiley, pp.560

13 Neuroglia in Caenorhabditis elegans

C. elegans has 302 neurons and 56 glial cells. Glial cell types:50 cells cover dendrites of sensory neurons; 4 of these 50 (CEP sheath glia) envelop the nerve ring and send processes to some synaptic sites in the brain. 6 cells (GLR glia) form gap junctions to both muscle cells and motor neurons.

Artificial ablation of glia in C. elegans does not kill neurones but greatly affects their development (neuronal assembly and neurite morphogenesis) and function

Bacaj, T, Tevlin, M, Lu, Y & Shaham, S, (2008): Science 322, 744-747.

C. elegans glia may also have sensory functions(from Shai Shaham laboratory webpagehttp://shahamlab.rockefeller.edu/research.php)

Calcium signalling in C.elegans glia is controlled mainly by voltage-gated Ca channels (Vlad Parpura, personal communication.

The ancestral glia retains some neuronal features

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Neuroglia in leech (Annelida)

Glial cell types:Packet glial cells(ensheath neuronalsomatas) Connective glial cells(ensheath axons)Giant glial cells(form neuropil and provide for ion and neurotransmitter homeostasis)All glial cells are coupled through gap junctions and form a panglial syncytium

Giant glial cell Neuronal cell bodies

Outer capsule

Packet glial cell

Neuropil Inner capsule

Side nerve

Deitmer, Rose, Munsch, Schmidt, Nett, Schneider & Lohr (1999): Glia, 28, 175 - 182

Functions:

Metabolic supportControl over ion andneurotransmitter homeostasis

15 Neuroglia in insects (Arthropoda)

Glial cell types:Surface gliaCortex glia Neuropile gliaTract glia

Further diversity:Optic lobe glia

Fenestrated gliaPseudocartridge gliaSatellite gliaEpithelial gliaMarginal glia

Glia of the deeper optic lobe regionsGlia of the olfactory systemGlia of the antennaMushroom body glia

Main functions:Formation of blood-brain barrierTransport of substances from haemolymph to neuronesCompartmentalisation of the nervous systemNeurotransmitter homeostasis (histamine and glutamate)Ion homeostasisTrophic supportNeuroprotection (especially of dopaminergic neurones)Circadian rhythmsDevelopment of the CNSReactive gliosisPhagocytosis

Evolutionary advances:1) Great increase in morphological/functional diversity2) New function (BBB; compartmentalisation)3) Removal of glia kills neurones

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Neuroglia in vertebrates

Main Glial cell types:AstrocytesOligodendrocytes Radial gliaNG2 cellsMicrolgiaPeripheral glia (Schwann cells)

Great morphological and functional diversity

Profound morpho-functional heterogeneity of neuroglia between various brain regions and within regions

Main functions:Development of CNS/PNSControl over blood-brain barrierMain homeostatic elements of the brain(metabolic, transport, control over ions and neurotrasnmitters etc.)MyelinationBrain defenceHigher brain functions

Evolutionary advances:Neuroglia becomes main homeostatic/defensive system of the brain

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Evolution of myelination

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Early evolutionary roots of myelin sheath and fast action potential propagation

Action potential propagation velocity is the highest in prawns and shrimpswhere it reaches 180 – 210 m/s; in humans the fastest fibres conduct with a speed of ~100 – 120 m/s

Xu &Terakawa (1999): J Exp Biol 202,:1979-1989

19 Early evolutionary roots of myelin sheath and fast action potential propagation

The giant prawns, the Anomalocaris, where the largest and the most ferociouspredators of the Cambrian period (500 - 540 millions years ago) oceans; they were> 1 meter long and had exceedingly complex composite external eyes withcomposed from tens of thousands of hexagonal ommatidial lenses.

Paterson, Garcia-Bellido, Lee, Brock, Jago, Edgecombe (2011): Nature, 480, 237-240

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Myelin sheath increases the speed of action potential propagation 21 Oligodendroglia – myelinating cells of the CNS 22

Without myelination each human optic nerve would have a diameter of 0.75 m

Kettenmann & Verkhratsky, 2011

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The NG2 Glia – the cells of oligodendrogliallineage with an unknown function

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NG2 glia – enigmatic “fifth” glial element25

NG2 glia are present throughout the brain26

NG2 glial cells receive proper glutamatergic synapses27 Peripheral glia 28

Types of Schwann cells29 Morphology of Schwann cell 30

Satellite glia: homeostatic cells of sensory and sympathetic ganglia31 Enteric nervous system 32

Enteric glia integrates cellular elements of the gut 33 Olfactory system 34

Olfactory encheathing glial cells35