Myelination

Question 1

What increases the speed of action potential conduction?

Answer 1

• larger size
• Increased body temperature
• Fatty Insulation

Question 2

What is myelin?

Answer 2

A specialised membrane sheath surrounding most vertebrate axons.
It insulates axons from each other and speeds the conduction of nervous impulses.

Question 3

What are the gaps between sections of myelin called?

Answer 3

Nodes of Ranvier
Action potential jumps between these nodes

Question 4

A myelin sheath is composed of many loops of a _ process

Answer 4

Glial

Question 5

Oligodendrocytes produce (multiple/one) and Schwann cells produce (multiple/one) myelin sheath(s)

Answer 5

Multiple, one

Question 6

Derivation of Schwann cells

Answer 6

They are derived from the neural crest and migrate and differentiate under the control of peripheral axons.

Question 7

Derivation of oligodendrocytes

Answer 7

derived from progenitors that reside in the ventricular zone of the neural tube.
These precursors can form other cells, but really only considered to lead to oligodendrocytes.
They proliferate, migrate and then differentiate to become cells that can myelinate other axons

Question 8

Where do oligodendrocytes come from?

Answer 8

The region/stem cells of the spinal cord that previously gave rise to somatic motor neurons.
In the forebrain oligodendrocytes arise from ventral regions similar to spinal cord.

Question 9

True or false:
Immature oligodendrocytes can migrate, but adult ones cannot

Answer 9

True
Mature oligodendrocytes cannot migrate, therefore there is long-distance migration of precursors from restricted ventral foci in the neural tube

Question 10

Migration of oligodendrocyte precursors

Answer 10

Long-distance migration of precursors from restricted ventral foci in the neural tube.
They follow radial glia outwards and follow developing axon pathways longitudinally.
These precursors require cell adhesion molecules for migration.

Question 11

What signalling takes place when an oligodendrocyte reaches its target axon?

Answer 11

Kept alive by neuregulin growth factor family NRG1-3 with isoforms e.g. Glial growth factor GGF.
These ligands bind receptors (ErbB) on undifferentiated neural crest cells that contact axons which sets off a Ras-Raf-MAPK signalling pathway.

Question 12

True or false:
The axon has to be electrically active for myelination to occur

Answer 12

True
They provide mitogenic signals for O2A (NG2) cells such as PDGF, and neuregulin

Question 13

There is negative regulation of oligodendrocytes differentiation via _ signalling

Answer 13

Notch

Question 14

Signals from neurons enhance myelin gene transcriptase so that thicker axons get _ myelin.

Answer 14

Thicker

Question 15

Route of migration of Schwann cells

Answer 15

Migrate over the surface of the neural tube and then through the anterior somites.
They follow similar pathways to reach their correct locations.

Question 16

How do Schwann cells produce a myelin sheath?

Answer 16

The myelin sheath is generated by continued migration of the processes leading edge around the axon. While the leading glial process continues to encircle the axon, the earlier-formed loops undergo compaction to form the contact myelin sheath.

Question 17

What happens when immature schwann cells meet the axon?

Answer 17

Immature cells interact with axons and signally occurs, with the right signally they will begin myelinating.
Some (non-myelinating) don’t do this, just keep axon from being myelinated.

Question 18

What do neuregulins do?

Answer 18

They stimulate differentiation and proliferation of Schwann cell precursors.
For example GGF (glial growth factor)

Question 19

What is Krox20?

Answer 19

zinc-finger transcription factor.

Knockout of this gene causes no myelinating Schwann cells.
Signals from axons (neuregulins) upregulate Krox20 in Schwann cell precursors that contact them.

Question 20

What is Pax3?

Answer 20

paired domain transcription factor.

Inhibits Schwann cell differentiation.
Expressed in SC progenitors and downregulated as myelination starts.
Controls expression of e.g., MBP (myelin basic protein).

Question 21

What is L1?

Answer 21

another Ig-class cell adhesion molecules

L1 is required for initiation of myelination in Schwann cells
Oligodendrocytes express a closely related cell adhesion molecule, neurofascin-155, at start of myelination - may ‘replace’ L1.
Downregulated after myelination starts

Question 22

What is Myelin-associated glycoprotein (MAG)?

Answer 22

Myelin-associated Glycoprotein MAG and a cytoskeletal-linking protein, periaxin, are initially located in Schwann cell membranes in contact with axon.
May modulate interaction, but periaxin not in oligodendrocytes.

Question 23

Dependence in mature Schwann cells

Answer 23

In mature Schwann cells, there is a looser dependence in neuregulins and instead they are dependent on neurotrophin-3, insulin-like growth factor 2 and platelet-derived growth factor-BB.

Question 24

What does autocrine survival allow Schwann cells to do?

Answer 24

Survive the death of the axon and retain the ability to stimulate nerve regrowth.

Question 25

True or false: Schwann cells can make myelin in culture alone

Answer 25

False Schwann cells must be in contact with an axon, but oligodendrocytes can make myelin in culture

Question 26

What is P0?

Answer 26

Present in Schwann cells only A cell adhesion molecule (Ig family). Links across myelin layers to stabilise them Required for compaction/stability of myelin Most abundant protein in PNS myelin

Question 27

What is proteolipid protein (PLP)?

Answer 27

Almost entirely oligodendrocytes only Required for compaction/stability of myelin Most abundant protein in CNS myelin

Question 28

Is myelin basic protein (MBP) associated with oligodendrocytes or Schwann cells?

Answer 28

Both

Question 29

During formation of the myelin sheath, where does Na+ cluster?

Answer 29

Where the node of Ranvier will be, effects where the myelin sheath will end.

Question 30

What is the paranode?

Answer 30

The site of tight axon-glial adhesions. There is a thin axo-glial space at the paranode loops that creates a high node-internode periaxonal resistance which electrically isolates the internodal membrane. Since this resistance is so high, the charging of the internodal membrane is very slow and so the change in Vm at the internode is insignificant.

Question 31

Clustering of sodium channels throughout myelination

Answer 31

Sodium channels cluster early at wide immature nodes. As these nodes narrow and mature, sodium channel density increases.

Question 32

Potassium channel clustering during myelination

Answer 32

Potassium channels cluster later at the nodes and shift their position to the paranode and then the juxtaparanode as the structure matures.

Question 33

Characteristic of juxtaparanodal regions

Answer 33

K+ channels are highly concentrated

Question 34

What does the binding of oligodendrocytes or Schwann cells to axons do to the clustering of channels?

Answer 34

Regulates the clustering of sodium channels to the node and potassium channels to the paranode. Presumably a consequence of specific protein-protein contacts in the paranodal loops.