Glia & Myelin - Drewes

Question 1

What is myelin according to Dr. Drewes?

Answer 1

Extension of lipid membrane of Oligodendrocyte cells that covers axons.

Question 2

What is myelin composed of?

Answer 2

Lipid (70%) & Protein (30%)

Question 3

Is myelin ester-linked or ether-linked?

Answer 3

Ether-linked

Question 4

What 6 prominent proteins are found in CNS myelin?

Answer 4

1. MBP (myelin basic protein)
2. PLP (proteolipid protein)
3. CNP (cyclic neucotide P-ase)
4. MAG (Myelin associated glyprot)
5. MOG (Myelin-Oligoden. Glycoprot)
6. OMgp (Oligoden.-Myelin-Glycoprot)

(only memorize the first three, because the rest all contain “myelin” in the name)

Question 5

What are the two proteins that are different in PNS myelin compared to CNS?

Answer 5

• P₀(P₀prot) instead of PLP
• 7th protein = PMP-22

Question 6

What does MBP do in the CNS myelin?

Answer 6

“Glues” together the first and second lipid bilary when they come close.

Question 7

What does PLP do in the CNS myelin?

Answer 7

Brings together extracellular components of 2nd lipid bilayer and on.

-PLP is a membrane spanning protein that has affinity for other PLPs on the other membranes

Question 8

Where is cholesterol present in myelin?

Answer 8

Both leaflets of the lipid bilayer.

Extracellular - Galactose/sulfoGalactose

Intracellular - P-inositol/P-serine

Question 9

What does it mean when Dr. Drewes says that “Myelin is inert.”?

Answer 9

• formed when we are young
• very low turnover
• recent studies actually indicate that there is some activity

Question 10

What cells give rise (are precursors) to oligodendrocytes?

Answer 10

OPCs

Question 11

Why do OPCs remain in the adult brain long after myelination is complete?

Answer 11

OPCs make oligodendrocytes in adult brain in response to injury/demyelinating diseases (e.g. MS).

Question 12

What is the difference between demyelinating and dysmyelinating?

Answer 12

• Demyelinating:
  
  • have normal myelin, but then some disease leads to breakdown
• Dysmyelinating:
  
  • the myelin was never formed right to begin with –> defective due to inherited genetic mutation

Question 13

Experimental Allergic Encephalomyelitis (EAE) is a model for what common disease?

Answer 13

MS

Question 14

Experimental Allergic Neuritis (EAN) is a model for what disease?

Answer 14

Guillain-Barré Syndrome

(immunity against peripheral components of myelin)

Question 15

Where is the mutation in adrenoleukodystrophy that allows synthesis of long chain fatty acids, but is blocked by Lorenzo’s Oil?

Answer 15

ABC transporter

Question 16

What does PLP do in myelin?

Answer 16

Acyl groups make it lipid soluble

Question 17

What is the result if any of the exons in Myelin Basic Protein (MBP) are misread?

Answer 17

Myelin disorder

(result of gene duplication or overproduction)

Question 18

What creates the water accumulations that MRI scans detect in MS lesion?

Answer 18

Demyelination –> breakdown of lipid & proteins –> less lipid means more water present due to less fat

Question 19

What allows white blood cells to attach and penetrate blood vessels after stimulation by cytokines?

Answer 19

Vascular Cell Adhesion Molecule

Question 20

What does Mab do in treatment of MS with Natalizumab?

Answer 20

Blocks immune cells from getting into the brain!

(antibody against alpha-4-beta-1 receptor on white blood cell)