Oligodendrocytes and Schwann Cells

Question 1

Why is the brain’s white matter white?

Answer 1

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

Question 2

Which progenitor cells do oligodendrocytes develop from?

Answer 2

O-2A progenitor cells

Question 3

Name an oligodendroglial and astroglial biomarker

Answer 3

Oligodendroglial: Galactocerebroside
Astroglial: Glial fibrillary acidic protein (GFAP)

Question 4

A 1988 experiment showed that type1 astrocytes could induce O-2A cell proliferation in culture. Which key factor were the astrocytes releasing?

Answer 4

Platelet-derived growth factor (PDGF)

Question 5

Which PDGF receptor do O-2A cells express?

Answer 5

PDGFRalpha - as they bind both PDGF-AA and PDGF-BB, and the PDGFRbeta does not have affinity to the PDGF-AA ligand

Question 6

In which part of the spinal cord do the earliest oligodendrocyte precursors originate?

Answer 6

A restricted section of the ventricular zone

Question 7

In which part of the embryonic brain do the earliest oligodendrocyte precursors originate?

Answer 7

A localised germinal zone in the ventral diencephalon

Question 8

Name a marker for both immature and mature oligodendrocytes, and a marker for mature oligodendrocytes only

Answer 8

Both: O4

Mature only: GSTn

Question 9

The transcription factors Olig1 and Olig2 are both involved in oligodendrocyte development. Which is essential?

Answer 9

Olig2

Question 10

Which other cell lineage is generated under the influence of Olig2, and which other transcription factors are involved?

Answer 10

Motor neurons - with the addition of Ngn1 and Ngn2

Question 11

The embryonic spinal cord has two apposing morphogen gradients. Name the two substances produced and their gradients

Answer 11

Sonic hedgehog (SHH) from the floor plate, ventral to dorsal gradient
Bone morphogenic protein 4 (BMP4) from the roof plate, dorsal to ventral gradient

Question 12

Which of SHH and BMP4 promotes oligodendrocyte development, and which inhibits it?

Answer 12

SHH promotes (and is essential for oligodendrocyte development)
BMP4 inhibits

Question 13

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?

Answer 13

Netrin-1 and sema3a, released by the optic chiasm

Question 14

How does electrical stimulation of CNS neurons affect their myelination?

Answer 14

It increases it

Question 15

Describe the relationship between activated neurons, astrocytes, and oligodendrocytes

Answer 15

Activated neurons release ATP, which stimulates astrocytes to produce leukaemia inhibitory factor (LIF). LIF promotes myelination by mature oligodendrocytes

Question 16

Why do oligodendrocytes on transected axons die?

Answer 16

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

Question 17

Which area of the spinal cord do most oligodendrocytes develop from?

Answer 17

Ventral spinal cord

Question 18

Name three cell adhesion molecules released by axons to stimulate oligodendrocytes and cause myelination

Answer 18

Neuregulin, NCAM, and L1

Question 19

Name three inhibitory molecules downregulated by axons to stimulate myelination by oligodendrocytes

Answer 19

Notch, PSA-NCAM, and lingo-1

Question 20

The process of myelination involves two motions. What are they?

Answer 20

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

Question 21

Where in the axon do sodium channels cluster?

Answer 21

Nodes of Ranvier

Question 22

Give two differences between oligodendrocytes and Schwann cells

Answer 22

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

Question 23

Describe the propagation of an action potential in an unmyelinated axon

Answer 23

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

Question 24

Name the type of conduction that takes place in myelinated axons

Answer 24

Saltatory conduction

Question 25

Name the two types of nerve fibres which convey pain

Answer 25

A-delta and C fibres

Question 26

Which type of nerve fibres are unmyelinated?

Answer 26

C fibres

Question 27

Which type of nerve fibre conveys motor information?

Answer 27

A-alpha

Question 28

Which type of nerve fibre conveys autonomic information?

Answer 28

B

Question 29

What are Remak bundles?

Answer 29

Nerve fibres surrounded by Schwann cells but not by myelin

Question 30

What is the function of a Remak bundle?

Answer 30

To provide structural support

Question 31

Where do Schwann cells originate embryonically?

Answer 31

The neural crest

Question 32

Can Schwann cells survive without neurons?

Answer 32

No

Question 33

Can neurons survive without Schwann cells?

Answer 33

No - they can develop but quickly die

Question 34

Name a key factor in Schwann cell survival

Answer 34

Neuregulin 1 type III

Question 35

What happens when neuregulin 1 type III is overexpressed?

Answer 35

Previously unmyelinated axons - e.g. C fibres - become myelinated, and already myelinated axons become too thickly myelinated

Question 36

Name a transcription factor expressed by myelinating but not non-myelinating Schwann cels

Answer 36

Krox-20

Question 37

What is the main sodium channel at the nodes of Ranvier?

Answer 37

Nav1.6

Question 38

Which sodium channel is only expressed in unmyelinated pain neurons?

Answer 38

Nav1.8

Question 39

What are lipid rafts and what do they do?

Answer 39

Cholesterol and sphingolipid-enriched membrane microdomains, involved in signal transduction and endocytosis - sorting and localisation of proteins

Question 40

What happens when lipid rafts are disrupted?

Answer 40

The propagation of action potentials is blocked, leading to loss of responsiveness to pain stimuli

Question 41

What is the most common inherited neurological disorder?

Answer 41

Charcot-Marie-Tooth disease

Question 42

What is Charcot-Marie-Tooth disease?

Answer 42

A group of inherited disorders of the PNS, characterised by progressive loss of muscle tissue and touch sensation across various parts of the body

Question 43

What is Guillain-Barre syndrome?

Answer 43

An infection-induced inflammatory nerve disorder in which the immune system attacks the PNS, causing rapid-onset muscle weakness

Question 44

What causes Guillain-Barre syndrome?

Answer 44

Infection - typically with Campylobacter jejuni - leading to the development of antibodies against gangliosides, which damage the myelin sheath

Question 45

Define the focal lesion model of axon damage

Answer 45

Focal lesions trigger Wallerian degeneration of distal axons while proximal axons remain intact

Question 46

Describe Wallerian degeneration

Answer 46

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

Question 47

How do astrocytes inhibit axon regrwoth after injury?

Answer 47

They synthesise glial fibrillary acidic protein (GFAP) and form a glial scar, blocking axonal growth

Question 48

Name five proteins upregulated in denervated Schwann cells

Answer 48

p75NTR, NGF, BDNF, GFAP, glial maturation factor beta, LP, NCAM, L1

Question 49

Name three proteins downregulated in denervated Schwann cells

Answer 49

Myelin-association proteins (MAPs), e-cadherin, Krox-20