Glia and Myelin

Question 1

What cells make the myelin in the CNS? PNS?

Answer 1

CNS - oligodendrocytes (wrap around multiple axons)

PNS - Schwann Cells (wrap around one axon each)

Question 2

What part of the schwann cell is actually extending and wrapping around the axon?

Answer 2

It’s actually the layer that’s closest the axon

Question 3

In terms of percentages, what is the protein and lipid content of myelin?

Answer 3

70% lipid and 30% protein

(which is opposite from other plasma membranes elsewhere in the body)

Question 4

What are the 3 molecules contributing the most fo the lipid portion of the myelin?

Answer 4

cholesterol

galactolipid

phospholipid

Question 5

The proteins found in myelin are pretty similar between the CNS and PNS. What two proteins are only in one or the other, not both?

Answer 5

proteoLipid Protein (PLP) is in the CNS

P0 is in the PNS

Question 6

Is the lipid composition symmetric across the lipid bilayer in myelin?

Answer 6

No - it’s asymmetric composition

Question 7

As the layers of myelin wrap around each other, they squeeze water out. WHat molecule is left to be the “glue” between the layers?

Answer 7

myelin binding protein (MBP)

Question 8

In the CNS, what is the transmembrane protein that acts sort of like velcro between the layers of myelin? In the PNS?

Answer 8

CNS - Proteolipid protein

PNS - P0

Question 9

What are the two general classes of white matter diseases in the CNS? How do they differ?

Answer 9

Demyelination - maintly aquired (MS is the big one); you have normal myelin that’s being broken down

Dysmyelinating - mainly inherited (leukodystrophies); the myelin was never normal to begin with

Question 10

What are the two general classes of myelin disorder neuropathies in the PNS?

Answer 10

acquired (mainly autoimmune demyelinating diseases)

hereditary (mainly dysmyelinating, like charcot marie tooth)

Question 11

What are the two main proteins of myelin that have mutations leading to disease?

Answer 11

PLP (jimpy, rumpshaker mutations)

MBP (shiver mutation)

Question 12

Why is the shiverer mutation so significant?

Answer 12

It was the first successfull gene therapy in an animal

Question 13

What protein is affected in Charcot-Mari-Tooth Disease?

Answer 13

it’s a genetic duplication of the PMP22 gene

this means you get too much PMP22 protein produced, which causes an issue with myelin synthesis

Question 14

How do we create models for MS and Guillain-Barre Syndrome in mice?

Answer 14

Injecting myelin form one mouse into a different mouse will lead to an immune response that will then cross react with the second mouse’s own myelin

MS: inject central myelin = experimental allergic encephalomyelitis

Guillain-Barre Syndrome: inject peripheral myeoin = experimental allergic Neuritis

Question 15

Why to MS plaques appear white on MRI?

Answer 15

MRI detects protons of water molecules

myelin that is normally wrapped wil extrude any water, so it will appear black on MRI. However, in MS the myelin is disrupted, allowing water to seep back thorugh and light up on MRI

Question 16

Describe has the Natalizumab treatment works for MS?

Answer 16

It’s antibodies against the integrin alpha4

alpha4 is present on leukocytes and is the receptor that binds to the VCAM adhesion molecules on the vessel endothelial walls in order for the leukocyte to diapedese into the brain

antibodies block their ability to enter the brain tissue, thus decreasing the number of plaques

Question 17

When during humand evelopment does myelination occur?

Answer 17

Infants actually have very little myelin in their brains - it expands and grows hugely during the first few years of life