Oligodendrocytes and Schwann Cells Flashcards
Describe the steps in the development of the oligodendrocyte from early precursor to myelinating cell Discuss how the number of oligodendrocytes becomes matched to the number of axons requiring myelination Contrast oligodendrocyte development and function with Schwann cell development and function
Why is the brain’s white matter white?
The white matter is mainly made up of lipids in the form of myelin. Myelin is very thin without much mass, hence the white colour
Which progenitor cells do oligodendrocytes develop from?
O-2A progenitor cells
Name an oligodendroglial and astroglial biomarker
Oligodendroglial: Galactocerebroside
Astroglial: Glial fibrillary acidic protein (GFAP)
A 1988 experiment showed that type1 astrocytes could induce O-2A cell proliferation in culture. Which key factor were the astrocytes releasing?
Platelet-derived growth factor (PDGF)
Which PDGF receptor do O-2A cells express?
PDGFRalpha - as they bind both PDGF-AA and PDGF-BB, and the PDGFRbeta does not have affinity to the PDGF-AA ligand
In which part of the spinal cord do the earliest oligodendrocyte precursors originate?
A restricted section of the ventricular zone
In which part of the embryonic brain do the earliest oligodendrocyte precursors originate?
A localised germinal zone in the ventral diencephalon
Name a marker for both immature and mature oligodendrocytes, and a marker for mature oligodendrocytes only
Both: O4
Mature only: GSTn
The transcription factors Olig1 and Olig2 are both involved in oligodendrocyte development. Which is essential?
Olig2
Which other cell lineage is generated under the influence of Olig2, and which other transcription factors are involved?
Motor neurons - with the addition of Ngn1 and Ngn2
The embryonic spinal cord has two apposing morphogen gradients. Name the two substances produced and their gradients
Sonic hedgehog (SHH) from the floor plate, ventral to dorsal gradient Bone morphogenic protein 4 (BMP4) from the roof plate, dorsal to ventral gradient
Which of SHH and BMP4 promotes oligodendrocyte development, and which inhibits it?
SHH promotes (and is essential for oligodendrocyte development) BMP4 inhibits
The migration of oligodendrocyte precursor cells along the path of the optic nerve is controlled by two chemorepellants. Where are they released from, and what are they?
Netrin-1 and sema3a, released by the optic chiasm
How does electrical stimulation of CNS neurons affect their myelination?
It increases it
Describe the relationship between activated neurons, astrocytes, and oligodendrocytes
Activated neurons release ATP, which stimulates astrocytes to produce leukaemia inhibitory factor (LIF). LIF promotes myelination by mature oligodendrocytes
Why do oligodendrocytes on transected axons die?
Oligodendrocytes die unless supplied with neuregulin. Neuregulin is produced by neuronal axons and attaches to receptors on oligodendrocytes. When axons are transected, they die and stop producing neuregulin
Which area of the spinal cord do most oligodendrocytes develop from?
Ventral spinal cord
Name three cell adhesion molecules released by axons to stimulate oligodendrocytes and cause myelination
Neuregulin, NCAM, and L1
Name three inhibitory molecules downregulated by axons to stimulate myelination by oligodendrocytes
Notch, PSA-NCAM, and lingo-1
The process of myelination involves two motions. What are they?
1) Wrapping of the leading edge of an oligodendrocytic process around the axon underneath the previously deposited membrane
2) Lateral extension of the myelin membrane towards the nodal regions
Where in the axon do sodium channels cluster?
Nodes of Ranvier
Give two differences between oligodendrocytes and Schwann cells
Oligodendrocytes myelinate axons in the CNS, whereas Schwann cells myelinate axons in the PNS
Oligodendrocytes produce multiple myelin sheaths and myelinate multiple axons, whereas Schwann cells have a 1:1 relationship with an axon segment
Describe the propagation of an action potential in an unmyelinated axon
Usually, uneven concentrations of ions give the axon membrane a negative resting potential. Stimuli cause an influx of sodium ions at that location, making that area relatively positive and producing an action potential and a local current. This triggers the opening of the adjacent sodium ion channel, leading to further propagation by sequential changes of local membrane potential
Name the type of conduction that takes place in myelinated axons
Saltatory conduction
Name the two types of nerve fibres which convey pain
A-delta and C fibres
Which type of nerve fibres are unmyelinated?
C fibres
Which type of nerve fibre conveys motor information?
A-alpha
Which type of nerve fibre conveys autonomic information?
B
What are Remak bundles?
Nerve fibres surrounded by Schwann cells but not by myelin
What is the function of a Remak bundle?
To provide structural support
Where do Schwann cells originate embryonically?
The neural crest
Can Schwann cells survive without neurons?
No
Can neurons survive without Schwann cells?
No - they can develop but quickly die
Name a key factor in Schwann cell survival
Neuregulin 1 type III
What happens when neuregulin 1 type III is overexpressed?
Previously unmyelinated axons - e.g. C fibres - become myelinated, and already myelinated axons become too thickly myelinated
Name a transcription factor expressed by myelinating but not non-myelinating Schwann cels
Krox-20
What is the main sodium channel at the nodes of Ranvier?
Nav1.6
Which sodium channel is only expressed in unmyelinated pain neurons?
Nav1.8
What are lipid rafts and what do they do?
Cholesterol and sphingolipid-enriched membrane microdomains, involved in signal transduction and endocytosis - sorting and localisation of proteins
What happens when lipid rafts are disrupted?
The propagation of action potentials is blocked, leading to loss of responsiveness to pain stimuli
What is the most common inherited neurological disorder?
Charcot-Marie-Tooth disease
What is Charcot-Marie-Tooth disease?
A group of inherited disorders of the PNS, characterised by progressive loss of muscle tissue and touch sensation across various parts of the body
What is Guillain-Barre syndrome?
An infection-induced inflammatory nerve disorder in which the immune system attacks the PNS, causing rapid-onset muscle weakness
What causes Guillain-Barre syndrome?
Infection - typically with Campylobacter jejuni - leading to the development of antibodies against gangliosides, which damage the myelin sheath
Define the focal lesion model of axon damage
Focal lesions trigger Wallerian degeneration of distal axons while proximal axons remain intact
Describe Wallerian degeneration
The process of axon degeneration distal to a site of transection. This involves dissociation of the myelin sheath, removal of myelin and axonal debris by macrophages, removal of myelin-associated molecules which inhibit axonal growth, proliferation of glial cells distal to the injury, and growth factor secretion from these glial cells, attracting axonal sprouts from the proximal stump
How do astrocytes inhibit axon regrwoth after injury?
They synthesise glial fibrillary acidic protein (GFAP) and form a glial scar, blocking axonal growth
Name five proteins upregulated in denervated Schwann cells
p75NTR, NGF, BDNF, GFAP, glial maturation factor beta, LP, NCAM, L1
Name three proteins downregulated in denervated Schwann cells
Myelin-association proteins (MAPs), e-cadherin, Krox-20
