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Neuroglia and Myelin Dr. Raymond Colello

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1 Neuroglia and Myelin Dr. Raymond Colello

2 Glia Cell Classes Two Major Classes of Glia 1.) Macroglia Astrocytes
Oligodendrocytes Ependymal Cells 2.) Microglia

3 Function of Glia Cells Astrocytes - Structural support
- Induce tight junction formation by endothelial cells - Guide neuroblast migration and axon growth - Take up neurotransmitters within synaptic regions - Take up excess K+ released during high neuronal activity - Form a glial scar after CNS lesion Oligodendrocytes - Ensheath CNS axons with myelin - Locally regulate axon size - Stabilize axon numbers in a developing pathway Microglia - Serve as brain macrophages -Regulate astrocytes during development and injury Schwann Cells - Ensheath PNS axons with myelin

4 Distribution of glial cells in the CNS

5 Glial Cell Lineage MBP-positive A2B5-positive GFAP-positive

6 Growth factors control glial cell diversification
O-2A: Oligodendrocyte- Type 2 Astrocyte PDGF: Platelet-derived growth factor CNTF: Ciliary neurotrophic factor

7 Distribution of glial cells in the CNS

8 Astrocytes form the glial limiting membrane
Outer surface of CNS Phase Micrograph Immunostain for GFAP

9 Astrocytes establish blood brain barrier by inducing tight junction formation
Blood Vessel---- GFAP staining

10 Astrocytes guide neuroblasts to final destination
---Cerebellum ---Hippocampus

11 Astrocytes guide the migration of neuroblasts
Molecular Layer Granule cell Layer GFAP Immunostain

12 Guiding neuroblast migration

13 Astrocytes take up excess K+ during high neuronal activity

14 Astrocytes form gliotic scar following CNS injury
MRI of Spinal Cord Injury Green: GFAP Red: Chondroitin Sulfate Proteoglycans

15 Function of Glia Cells Astrocytes - Structural support
- Induce tight junction formation by endothelial cells - Guide neuroblast migration and axon growth - Take up neurotransmitters within synaptic regions - Take up excess K+ released during high neuronal activity - Form a glial scar after CNS lesion Oligodendrocytes - Ensheath CNS axons with myelin - Locally regulate axon size - Stabilize axon numbers in a developing pathway Microglia - Serve as brain macrophages -Regulate astrocytes during development and injury Schwann Cells - Ensheath PNS axons with myelin

16 Oligodendrocytes myelinate CNS axons
Oligodendrocytes can wrap up to 50 axons with myelin Each myelin sheath is made of up to 100 turns of myelin

17 Relationship between oligodendrocyte perikaryon and an unrolled myelin internode

18 Immunocytochemical distribution of myelin proteins
MBP: 30% of total protein PLP: 50% of total protein CNP: 5% of total protein MAG: 1% of total protein

19 Conduction velocity Myelinated versus Unmyelinated
A 4µm myelinated axons conducts at the same speed at a .5mm unmyelinated axon

20 Propagation of nerve impulse
Unmyelinated axons exhibit continuous conduction whereas myelinated axons exhibit saltatory conduction

21 Destruction of oligodendrocytes leads to demyelinating diseases
Plaque Demyelinated plaques found in the dorsal columns Of the spinal cord

22 Does the CNS have the capacity to regenerate?

23 Testing the peripheral and central nervous system environment
Axons of CNS neurons will grow through peripheral nerve bridge but will not enter CNS bridge. Something n the CNS is inhibitory for neurite outgrowth.

24 Testing inhibitory properties of CNS cells
RGC’s on astrocytes RGC’s on oligodendrocytes

25 Identifying myelin inhibitor

26 Neutralizing oligodendrocyte inhibitor promotes regeneration
  Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME Nature Nov 30;378(6556): Nature Jan 27;403(6768):434-9. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME.

27 Know the different classes of glial cells and what are their
distinguishing features Know glial cell lineage and the growth factors associated with glial cell differentiation Know glial cell function Know why the CNS shows little regenerative capacity


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