Neuroglia and Myelin Dr. Raymond Colello

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

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

Distribution of glial cells in the CNS

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

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

Distribution of glial cells in the CNS

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

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

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

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

Guiding neuroblast migration

Astrocytes take up excess K+ during high neuronal activity

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

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

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

Relationship between oligodendrocyte perikaryon and an unrolled myelin internode

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

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

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

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

Does the CNS have the capacity to regenerate?

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.

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

Identifying myelin inhibitor

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. 1995 Nov 30;378(6556):498-501. Nature. 2000 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.

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