DGN - Oligodendrocytes and other Myelinating Cells

Question 1

What are the 2 main types of myelinating cells?

Answer 1

1) Oligodendrocytes (all myelinating)

• In CNS
• Each myelinating multiple axons (average ~10 axons per cell)

2) Schwann Cells (myelinating and non-myelinating).

• Myelinating Schwann cells wrap single axons

Question 2

What influences Myelination?

Answer 2

Myelination is dependent on axonal diameter, and vice versa

Question 3

Explain the g-ratio of axons

Answer 3

The ratio of the number of myelin lamellae to the axon’s diameter, which remains constant in both CNS and PNS

Question 4

What is the Interdependence of glia-axons?

Answer 4

Where the loss of axons results in degeneration of oligodendrocytes and de-differentiation of Schwann cells

• conversely, axons degenerate in the absence of appropriate support from Schwann cells and oligodendrocytes

Question 5

Non-myelinating Schwann cells (3)
vs
Perisynaptic Schwann cells (at NMJ) (2)

Answer 5

Non-myelinating Schwann cells

• Surround bundles of small-diameter neurons
• Provide support and isolation from myelinated axons
• Express specific surface markers L1 and NCAM not found in myelinating Schwann cells

Perisynaptic Schwann cells (at NMJ)

• They respond to synaptic activity by Ca2+ waves
• Able to modulate synaptic activity by regulating extracellular ion levels and also inducing post-synaptic Ach receptor aggregation

Question 6

What are Olfactory Bulb Ensheathing Cells (OBECs)? (5)

Answer 6

• Similar to non-myelinating Schwann cells, ensheath the axons of the olfactory nerve
• Located at the interphase of the CNS and PNS
• They phagocytose axonal debris and dead cells
• OBECs support and guide olfactory axons, grow through glial scars, and secrete many neurotrophic factors
• OBECs express glial markers such as GFAP, s100, and p75, and radial glial markers such as nestin and vimentin

Question 7

What are 3 features of the myelin sheath?

Answer 7

• Fatty insulated later facilitates saltatory conduction
• The myelin sheath is wrapped around axons to form concentric layers of lamellae
• Longitudinally, myelin sheaths are separated by nodes of Ranvier: specialised naked axonal areas where action potentials are propagated. Myelin sheath between nodes called internodes

Question 8

What occurs next to the node of ranvier?

Answer 8

Molecular interactions at the Paranode and Juxtaparanode define the clustering of K+ and Na+ channels that are key for the saltatory conduction

Question 9

Explain the composition of the Myelin Sheath.

Answer 9

It consists mainly of lipids (70%) and proteins (30%), with specific ratios and types differing between CNS and PNS

Question 10

Name the proteins in CNS myelin and in PNS myelin?

Answer 10

CNS myelin

• MBP ( fuse the extracelullar and cytoplasmic faces)
• PLP

PNS myelin

• P0 (mediates fusion of lamellae)
• PMP22
• Cx32

MAG present in both PNS and CNS, important for axon-myelin interaction, binding to specific gangliosides on the axonal surface

Question 11

Describe the myelination process

Answer 11

It involves four phases: Axon contact, ensheathment, and establishment of internodal segments, followed by remodelling and maturation

Question 12

What occurs during Phase 1: Axon contact? (4)

Answer 12

• Only if axon grows thicker than 0.7mm (PNS) or 0.2mm (CNS) diameter
• Loss of NCAM from axonal surface triggers myelination. Similarly, L1 is expressed at premyelination, tagging axons to be myelinated (“ready for myelination”)
• Partner molecules in myelinating cells not completely resolved
• Contact with axons triggers differentiation of OPCs into Oligodendrocytes, starting to express myelin products (GalC, CNP, MBP, etc)

Question 13

What occurs during Phase 2: Axon ensheathment and establishment of internodal segments? (3)

Answer 13

• Extension of an initiator process that spirals along the axon (using MAG and PLP to “stitch”)
• Myelination of multiple axons, followed by remodelling phase when non-ensheathing processes are lost
• Initial clustering of Na+ channels at nodes of Ranvier

Question 14

What occurs during Phase 3/4: Remodelling and maturation? (3)

Answer 14

• Subsequent wraps of myelin are produced, which fuse to each other dependent on PLP and MBP
• Loss of non myelinating processes
• Maturation of nodes of Ranvier (synchronised expression of molecular pairs at axon and myelin)

Question 15

Explain the pathophysiology of Multiple Sclerosis

Answer 15

Autoimmune attack on CNS myelin, leading to demyelination, incomplete remyelination, and neurodegenerative effects

Question 16

How does BBB breakdown contribute to Multiple Sclerosis?

Answer 16

It allows immune cells, particularly T cells, to enter the CNS, triggering inflammation and damage

Question 17

What perpetuates chronic inflammation in Multiple Sclerosis?

Answer 17

T cells attack myelin, recruit other inflammatory cells, and cause BBB leakage, leading to a cycle of damage and inflammation

Question 18

What are the consequences of chronic inflammation in Multiple Sclerosis?

Answer 18

Swelling, macrophage activation, and damage driven by astrocytes and microglia