Lecture 6 Flashcards
What are two structural characteristics of myelin?
- lipid-rich, living insulating sheath
2. 50% dry weight of white matter
Where is myelin synthesized?
non-neuronal cells
Can myelin distribution change in learning and memory?
yes
Myelin surrounds some axons. Why?
High metabolic energy needed to produce myelin
Highly selective when wrapping around axon
What does myelin look like?
Dense staining wrapped around peripheral axon
Myelin gives white color to the white matter in the brain
Multi-layered membrane tightly wrapped and has light and dark lines
What is are differences between myelin wrapping between Schwann cells and oligodendrocytes?
Schwann: myelinates individual axons Cell is flattened out - flattened cytosol tubukar edge Oligodendrocytes: myelinates several axons or several parts of axons cell body is separate bumpy cytosol
What does compaction of the membranes contribute to?
Allows proteins to crosslink with each other
What does a dense line do?
Compresses together
What is periodicity?
Distance between lines composition of myelin is different between PNS and CNS
Why does myelin look like what it does?
- protein-lipid-protein repeats
- linked external proteins = intraperiod line (faint)
- linked internal proteins = major period (dense) line
- Periodicity
PNS: 11.9 nm
CNS: 10.7 nm
What is myelin composed of and at what proportions?
40% water
70-85% dry lipid
15-30% protein
What are the dry protein and dry lipid compositions in myelin, white matter and gray matter?
Myelin: 30% protein 70% lipid White matter: 39% protein 55% lipid Gray matter: 55% protein 33% lipid
What are the cholesterol, cerebrosides, galactolipid, plasmalogens, phospholipid compositions in lipid in myelin, white matter and gray matter?
Myelin:
28% cholesterol 23% cerebrosides 28% galactolipids 12% plasmalogens 43% phospholipids
White matter:
28% cholesterol 20% cerebrosides 29% galactolipids 11% plasmalogens 46% phospholipids
Gray matter
22% cholesterol 5% cerebrosides 7% galactolipids 9% plasmalogens 70% phospholipids
Which does myelin compositions more closely resemble; white matter or gray matter?
White matter
What happens when cerebrosides are lacking?
Myelin forms but develops vacuoles
Paralysis is seen in aged knockout mice because myelin starts to delaminate
When comparing between PNS and CNS, PNS has less _ and _ while CNS has more _.
cerebroside
sufatide
sphingomyelin
What are two major myelin proteins?
myelin basic protein (MBP) proteolipid protein (PLP)
What does a natural mutation of proteolipid protein lead to?
Jimpy mouse: "jerky" motor disturbance Very little myelin Die early Severe loss of oligos PLP produced is toxic
What is a milder knockout mouse of jimpy mouse?
Rumpshaker
no PLP toxicity
What does Myelin Basic Protein (MBP) induce and what can it be a model for?
Induces experimental allergic encephalomyelitis (EAE)
model for MS
What is a condition found when MBP is lacking?
shiverer mouse
What are enzymes found in myelin?
Cyclic nucleotide phosphodiesterase
Proteases
Lipid metabolism
Carbonic anhydrase
What do Ig like molecules contain?
Immunoglobin domain
What are Ig-like molecules found in myelin? What do they allow?
MOG and MAG
Oligo-axon communication
How much do PNS myelin protein take up in the PNS myelin? What is a major protein?
over 50%
P0
What happens when the PNS myelin protein is being knocked out?
Condition: Some Charcot-Marie-Tooth syndrome (CMT 1b)
Profound myelin defects
adhesion molecule compaction
PMP-22 is a PNS myelin protein. What gene produces it?
CMT 1a
What happens when CMT 1a is mutated?
Lethal
Tubular loop structure separate too much and widen the node of Ranvier
What is the onset age range for MS?
20s to 40s
What is vulnerable in MS patients?
Periventricular white matter
What is an example of axon demyelination?
axon-sparring
Where does demyelination occur in MS?
CNS
What is the female to male ratio in caucasians with MS?
1.5:1
What have linkage studies shown in MS?
Immunological factors involved
What do clusters/migration/geographic distribution suggest?
Environment
Vitamin D involvement
What virus can induce MS?
herpes
What activity degrades myelin in MS?
macrophage and protease
Name five types of therapies for MS?
- steroids
- interferons - interferes with immune system
- other immune suppressants
- hemopoietic stem cells
- dietary
Name examples of immune suppressants for MS?
cyclophosphamide antibodies e.g. alemtuzumab
What is a dietary factor in MS?
Vitamin D intake
What kind of infections can lead to Guillan-Barre syndrome?
Post viral/bacterial infections
e.g. campylobacter jejuni, zika virus (?)
What are symptoms if Guillan-Barre Syndrome?
Acute inflammatory response
Primary demyelination
Molecular mimicry
e.g. Between LPS of bacterial coat and myelin lipids/proteins
