Glia & Myelin - Drewes

Question 1

What does myelin do for a nerve?

Answer 1

Increases conduction velocity

Question 2

What happens in an abnormal evoked potential?

Answer 2

-It’s a study of nerve conduction velocity
-looks bumpy and delayed
MS patient - takes twice as long for electrical activity to get to the end. There is a delay in electrical conduction because myelin isn’t working as well

Question 3

What happens in an abnormal visual evoked potential?

Answer 3

• The response is delayed
• It takes longer for the signal to be received
• Latency time is 134

Question 4

What cells make myelin in what systems?

Answer 4

Oligodendrocytes (have large oddly shaped cell masses extending from nerve) in CNS
Schwann Cells (form perfect circle) in PNS

Question 5

When is myelination complete?

Answer 5

A few months after birth (very complete by early childhood)

Question 6

How much protein and lipid comprise myelin?

Answer 6

• 30% or less protein

- 70% or more lipid

Question 7

What is the composition of the membrane of a liver or heart cell?

Answer 7

• About 70% protein

- About 30% lipid

Question 8

What are the main subclass (not lipid or protein) of materials in myelin?

Answer 8

Mostly:

• cholesterol
• total galactolipid (more galactolipid than other membranes)
• total phospholipid

Question 9

In comparison to a membrane that isn’t myelin, myelin has?

Answer 9

A lot of cholesterol!

Question 10

What two things make up galactolipid?

Answer 10

Cerebroside & Sulfatide

Question 11

How are myelin lipids made?

Answer 11

1. Start as free fatty acids
2. Serine is added
3. Acyl group is added
4. Sugar is attached
5. Ex: if sugar is a galactose, its a galactoside

Question 12

What are the two very prominent proteins in CNS myelin?

Answer 12

MBP (myelin basic protein) & PLP (ProteoLipidProtein)

Question 13

What are these proteins?

• MBP (Myelin basic protein)
• PLP (ProteoLipidProtein)
• CNP (Cyclic Nucleotide P-ase)
• MAG (Myelin Associated Glyprot)
• MOG (Myelin-Oligoden. Glycoprot)
• OMgp (Oligoden.-Myelin-Glycoprot)

Answer 13

CNS Myelin Proteins

Question 14

What are these proteins?

• MBP
• P0
• CNP
• MAG
• MOG
• OMgp
• PMP-22

Answer 14

PNS Myelin Proteins

Question 15

What are the major lipids on the outer surface of myelin cells?

Answer 15

• Cholesterol
• GAlC
• sGalC

Question 16

What are the major lipids on the inner surface of myelin cells?

Answer 16

• P-inositol-4,5-diphosphate
• Ethanolamine plasmalogen
• P-serine

Question 17

What helps the two inner membranes (when cytoplasm comes together) stick? (in CNS & PNS)

Answer 17

MBP - protein used in layer when cell wraps twice

Question 18

What is the role of PLP in myelin (in CNS)?

Answer 18

It plays a significant role. It is a membrane spanning protein and has affinity for other PLPs on other membranes
-They bind the extracellular parts of membranes

Question 19

What is the role of P0 in myelin (in PNS)?

Answer 19

-P0 plays a role in extracellular compaction and MBP here helps with intracellular compaction (P2 - may play a role in , but we don’t know how it contributes)

Question 20

What makes myelin in the CNS?

Answer 20

Oligodendrocytes

Question 21

When does most myelination occur?

Answer 21

Early life

Question 22

What do OPCs (NG2) do?

Answer 22

Give rise to oligodendrocytes

Question 23

Many ? remain in the adult brain.

Answer 23

OPCs (Oligodendrocyte Precursor Cells)

Question 24

What do adults OPCs do?

Answer 24

They make become oligodendrocytes/make oligodendrocytes in adult brain in response to injury, demyelinating disease, MS, stroke, traumatic brain injury, etc.

Question 25

What do we keep in our brain on reserve waiting for a situation where we need more myelin?

Answer 25

OPCs - many in our brain in adulthood

Question 26

What happened in the mouse experiment when new OLs and myelin were blocked and a new motor skill was tested?

Answer 26

Poor motor skill/poor result

Question 27

What does the mouse experiment indicate?

Answer 27

Generation of new OLs and myelin is important for learning motor skills. (Mice can’t learn how to run very well without myelin.)

Question 28

How is the mouse experiment relevant to disease of myelin and psychiatric disease?

Answer 28

Disease of myelin - Relevant to adults with MS, brain trauma

Psychiatric disease - Have some myelination defects, some abnormalities in demyelination

Question 29

What are demyelinating diseases?

Answer 29

Means you already had healthy myelin before (ex: MS or others where you have a breakdown of myelin).
-Ex: MS, Guillain-Barre, etc.

Question 30

What are traits of a dysmyelinating disease?

Answer 30

• Mainly inherited
• Defect in creation of myelin since birth
• Ex: leukodystrophies, Charcot-Marie-Tooth

Question 31

What is the mouse model for MS?

Answer 31

Take myelin from one animal and put in another and the other animal will develop antibodies to it. Then these animals develop an immune response to their own myelin.

Question 32

What are other causes of demyelination in the CNS and/or PNS?

Answer 32

Radiation, infarct, tumors, toxins, drugs, infection

Question 33

What is EAE (Experimental Allergic Encephalomyelitis)?

Answer 33

Model for MS (mouse)

Question 34

What is EAN (Experimental Allergic Neuritis)?

Answer 34

Mode for Guillain-Barre Syndrome

Question 35

What is adrenoleukodystrophy (ALD)?

Answer 35

Dysmyelinating (mainly inherited)

• Movie made about it - Lorenzo’s Oil
• Treatment for condition = Lorenzo’s Oil, helped child live to 30
• Oil halts progression of disease by preventing body from producing long chain fatty acids whose buildup leads to demyelination

Question 36

What is the mutation in ALD?

Answer 36

Mutation in abcd1 transporter

-It transports long chain fatty acids into peroxisomes to be degraded

Question 37

What is PLP (proteolipidprotein)?

Answer 37

Various mutations in this gene make different myelination diseases

Question 38

What is the significance of Myelin Basic Protein (MBP)?

Answer 38

• 7 different axons make up myelin
• Alternative splicing makes different sizes of proteins - depending on how many spots are skipped, this determines the size of the protein
• RESULT of gene: to have many different proteins of different molecular weights - If any of these are misread, it leads to myelination disorder

Question 39

What happens in Charcot-Marie-Tooth on a molecular level?

Answer 39

-Muscle fades away bc it doesn’t have any neuronal input/stimulus
-Problem with PNP22 - This gene has been duplicated in the allele and it has twice as much of the protein product which is bad for myelin
Ex: Gene dosage causing a medical problem

Question 40

Why do you see white spots as the lesions in MS on an MRI?

Answer 40

• MRIs are detecting water (vibration of protons in water)
• More water = less fat = white spots where demyelination is occurring
• Cells are being attacked and myelin is being degraded (less fat) and then only the water shows up

Question 41

What is happening in MS on an immune cell level?

Answer 41

• Cells of immune system are attacking the brain
• These cells are penetrating the BBB by receptors and ligands on the endothelial cell
• VCAM1 is the receptor molecule and alpha4beta1 is the binding ligand on the T cells or macrophages

Question 42

How can we block T cells and macrophages from attacking in MS?

Answer 42

Make an antibody against alpha4beta1. Then the antibody binds here and prevents the cell from entering the brain (this is what Mab does!)

Question 43

What is natalizumab?

Answer 43

Mab! It is a treatment for MS.
-If you give Mab, you get fewer lesions since the treatment is blocking Tcells and macrophages from getting into the brain