Glia & Myelin - Drewes Flashcards by Kayla Schenheit

What does myelin do for a nerve?

Increases conduction velocity

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What happens in an abnormal evoked potential?

-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

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What happens in an abnormal visual evoked potential?

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

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What cells make myelin in what systems?

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

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When is myelination complete?

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

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How much protein and lipid comprise myelin?

30% or less protein

- 70% or more lipid

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

About 70% protein

- About 30% lipid

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

Mostly:

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

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

A lot of cholesterol!

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What two things make up galactolipid?

Cerebroside & Sulfatide

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How are myelin lipids made?

Start as free fatty acids
Serine is added
Acyl group is added
Sugar is attached
Ex: if sugar is a galactose, its a galactoside

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What are the two very prominent proteins in CNS myelin?

MBP (myelin basic protein) & PLP (ProteoLipidProtein)

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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)

CNS Myelin Proteins

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What are these proteins?

MBP
P0
CNP
MAG
MOG
OMgp
PMP-22

PNS Myelin Proteins

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

Cholesterol
GAlC
sGalC

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

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

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

MBP - protein used in layer when cell wraps twice

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

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

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

-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)

What makes myelin in the CNS?

Oligodendrocytes

When does most myelination occur?

Early life

What do OPCs (NG2) do?

Give rise to oligodendrocytes

Many ? remain in the adult brain.

OPCs (Oligodendrocyte Precursor Cells)

What do adults OPCs do?

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

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

OPCs - many in our brain in adulthood

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

Poor motor skill/poor result

What does the mouse experiment indicate?

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

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

Disease of myelin - Relevant to adults with MS, brain trauma | Psychiatric disease - Have some myelination defects, some abnormalities in demyelination

What are demyelinating diseases?

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

What are traits of a dysmyelinating disease?

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

What is the mouse model for MS?

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.

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

Radiation, infarct, tumors, toxins, drugs, infection

What is EAE (Experimental Allergic Encephalomyelitis)?

Model for MS (mouse)

What is EAN (Experimental Allergic Neuritis)?

Mode for Guillain-Barre Syndrome

What is adrenoleukodystrophy (ALD)?

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

What is the mutation in ALD?

Mutation in abcd1 transporter | -It transports long chain fatty acids into peroxisomes to be degraded

What is PLP (proteolipidprotein)?

Various mutations in this gene make different myelination diseases

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

- 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

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

-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

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

- 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

What is happening in MS on an immune cell level?

- 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

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

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

What is natalizumab?

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