Oligodendrocytes and Schwann Cells Flashcards
What are glial cells?
- Oligodendrocytes, schwann cells, astrocytes, microglia, satellite cells, ependymal cells
- In CNS and PNS but do not generate electrical impulses
- Support neurons (eg. guide extension of neuritis, maintain homeostasis of neurons, form myelin)
Compare oligodendrocytes and schwann cells
- Oligodendrocytes myelinate neurons in the CNS
- Schwann cells myelinate neurons in the PNS
- Schwann cells have a 1:1 ratio with an axon segment, while oligodendrocytes produce multiple myelin sheaths
What is the name of the gap between each myelin?
- Node of Ranvier
- In myelinated axons, electrical current jumps from one node of Ranvier to the next, which is called saltatory conduction
What are OPCs?
- Oligodendrocyte precursor cells
- Precursors to oligodendrocytes
Nature. 1983, 303(5916):390-6
- When optic nerves from 7-day-old rat were put in culture, astrocytes (in the presence of fetal calf
serum) and oligodendrocytes (in the absence of serum) can be obtained. - In certain culture conditions some of these cells acquire a mixed phenotype, displaying properties of both astrocytes and oligodendrocytes.
- These observations suggest that fibrous astrocytes and oligodendrocytes develop
from a common progenitor cell, thus named O-2A progenitor cells.
List factors in the development of oligodendrocytes
- O-2A progenitor cells (induced to proliferate by type 1 astrocytes via platelet derived growth factor)
- PDGF is used as a marker for OPCs. PGDF alpha receptors must be expressed on OPCs and O-2A.
- Olig2, neurogenin, sonic hedgehog, bone morphogenetic protein 4, netrin 1 and semma3a
List roles of oligodendrocytes
- Myelination which is vital to the correct functioning of the nervous system
- Correct ratio of oligodendrocytes to axons is essential during development for healthy axonal
growth - Dysmyelination during development usually leads to mental retardation and/or death
(leukodystrophies/leukoencephalopathies) - Energy efficient and space saving
- Axons also support oligodendrocytes survival
Describe development of schwann cells
- Schwann cells originate in the neural crest.
- Schwann cell precursors die under normal culture conditions and can be rescued by neuron conditioned
medium. - Unmyelinated axons are grouped together into Remak bundles, different from myelin.
- Neuregulin-1 type III is essential for both myelination and Remak bundles formation
Describe wallerian degeneration and remyelination
Wallerian Degeneration is a process of degeneration of the axon distal to a site of transection found by
Augustus Waller.
- Dissociation of myelin sheaths of distal axons
- Removal of the myelin and axonal debris by macrophages
- Removal of myelin-associated molecules, e.g. MAG, which would otherwise inhibit axonal growth
- During this process, proximal axons remain intact
- Glial cells distal to the injury proliferate
- Glial cells synthesize growth factors
- Secreted growth factors attract axonal sprouts from the proximal stump
Peripheral neurons can resprout after degeneration, while central neurons cannot, due to glial scar forming when astrocytes synthesise fibrillary acidic protein (GFAP).
Describe cues for oligodendrocytes to move during development
- When investigating the optic nerve, OPCs start in the 3rd ventricle, move to the chiasm and then towards the regina
- Moved by netrin 1 and semaphorin (Sema3a).
- They work as chemo repellents, pushing the OPCs away
- PVGF is also important, as a chemoattractant meaning the OPCs move towards i
- Leukaemia inhibitory factor is promoted by ATP released from activated neurons, which in turn promotes myelination by oligodendrocytes
Describe initiation of myelination
- Target innervaiton and electrical activity in the axon cause release of ATP
- ATP stimulates astrocytes to secrete leukaemia inhibitory factor
- Axons can directly stimulate oligodendrocytes through cell adhesion molecules (neuroregulin, NCAM, L1)
- Inhibitory molecules are downregulated (notch, PSA-NCAM, Lingo 1)
- Multiple axo-glial signals result in ensheathment
Describe myelin biogenesis in the CNS
2 motions:
- Wrapping of the leading edge at the inner tongue around the axon underneath the previously deposited membrane
- Lateral extension of myelin membrane layers toward the nodal regions.
Describe process of demyelination in MS
- Oligodendrocytes are generally absent from the centre of chronic lesions
- Bare axons surrounded by fibrous processes of astrocytes are seen in a chronic MS plaque
- Increased numbers at the ledion edge
- MOG expressing cells are found in large numbers at the edge of some MS lesions
What is the point of promoting remyelination?
- Restores myelin integrity and optimal saltatory conduction
- Reduced symptoms of MS attack
- Protect the axons in the long term
Describe the actions of innate macrophages during remyelination
- Clean up myelin debris by microglia, which inhibits remyelination
- Monocyte derived macrophages secrete pro-regenerative factors
