Myelin Flashcards

1
Q

What determines an axons speed

A

a) Capacitance and resistance of axonal membrane

Internal resistance of axonal cytosol (greater internal resistance = slower conduction velocity)

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2
Q

What is the length factor of an AP

A
  • The distance an AP may travel before it diminishes to an ineffective level
  • Determined by charge leakage
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3
Q

What is saltatory conduction in nerve fibres and how does it work?

A
  • To prevent need for wide nerve fibre, mammals adapted saltatory conduction: a process by which nerve impulses propagate along myelinated axons in a jumping fashion between NoR
  • Works due to the presence of insulatory myelin sheaths that allow fast conduction velocities while maintaining thin axons
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4
Q

What does myelin do and why is it good? brief

A
  • Myelin increases impulse propagation speed through sequestration of Na and K channels to the nodes of Ranvier
  • This reduces energy costs associated with regeneration of membrane potential
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5
Q

How is myelin produced?

A
  • Produced from myelinating glia cells;
    Oligodendrocytes in the CNS (can myelinate 10-20 cells); Schwann cells in the PNS (1:1 ratio with neurons)
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6
Q

What differs between Oligodendrocytes and Schwann cells

A

Oligodendrocytes
- Produced from the ventricular zone of the neuroepithelium
- Serves multiple axons
- Relies on the PLP protein

Schwann cells
- Originate from the neural crest in the sc
- Serve one axon
- Relies on P-zero protein

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7
Q

What is the process ‘Radial sorting’ and its coutcome?

A
  • During development, Schwann cells move along the length of axonal bundles in the sc
  • As they do this they proliferate and begin separating axons
  • Outcome separates axons into myelinating axons and Remak bundles - ‘cuffs’ of less myelinated, smaller calibre axons that bundle many cells together
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8
Q

How does the physical process of myelination occur?

A
  • Once a larger calibre axon has been sorted, the myelinating axon wraps it up
  • The inner MESAXON cuff will start to migrate AROUND the axon repeatedly to form a multi-layer structure (mediated by P-zero)
  • Inner mesaxonal cuff is driven by POLYMERISATION OF THE AXON cytoskeleton
  • Polymerisation results in infltion while depolymerisation results in deflation and therefore squeezing the cytoplasm forcing movement of the cell
  • Unknown stopping mechanism
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9
Q

What does myelin actually do?

A
  • Increases impulse propagation speed through sequestration of Na and K channels to the nodes of Ranvier (Saltatory conduction)
  • Reduction of energy cost associated with regeneration of membrane potential
  • Compact wiring
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10
Q

What are features of the following areas:
a) Nodal membrane
b) Paranodal junctions
c) Juxtaparanodal domain
d) Internode

A

a) the region of exposed axon membrane with a high concentration of Na+ and K+ channels

b) These are specialised regions adjacent to the NoR where the myelin sheath attaches to the axonal membrane. These consist of cell-adhesion complexes

c) Immediately adjacent to the paranodal junctions, extending away from the NoR. Contain a high concentration of K+ channels that are crucial in the refractory period of the AP

d) area covered by the myelin sheath

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11
Q

Contactin and Caspr are proteins at which junction? And with what glial protein do they form complexes?

A

Paranodal junctions and NF155

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12
Q

In Schwann cells in the PNS only, there are microvilli that are related to proteins that are instrumental in the direction of Na+ channels to the NoR

What proteins are involved in this process (3)

A

Cilia are enriched in GLIOMEDIN (just on glia) and NrCAM (on both glia and axon) form complexes with the axonal protein NF186

These molecules associate with Na+ channels directly

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13
Q

Building on the above card, briefly describe the mechanism of node formation in myelinated cells

A
  • Hemi nodal clustering of Na+ channels is the result of the paranodal complexes involving gliomedin, NrCAM and NF186
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14
Q

Peripheral neurons are not protected by a bony structure like CNS neurons are so they are endowed with other protective attributes.

What is the:
a) Epineurium
b) Perineurium
c) Endoneurium

and what are their attributes

A

a) Covers a number of fascicles made up of groups of peripheral nerves
b) Is the coating around one fascicle
c) Coating within the fascicle consisting of lots of collagen

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15
Q

What is Guillain-Barre Syndrome?

A
  • This is a peripheral condition in which the immune system attacks the peripheral nerves
  • Acquired after food poisoning because of antigenic mimicry of the bacterial surface proteins with neuronal surface proteins
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16
Q

Describe Charcot-Marie-Tooth Disease? (what gene / protein causes it)

A
  • Major cause of CMT is a duplication of chromosome 17 resulting in a triple dose of gene PMP22 that codes a myelin integrin protein (61% of CMT cases)
  • This duplication causes destabilisation of the myelin sheath
  • Reduced efficiency sequestering Na+ and K+ channels
  • Key feature = muscle wastage - result of death of unmyelinated axons
17
Q

There are multiple types of CMT. What are they and what causes them? (tough)

A

CMT1A: Duplication of gene on chromosome 17, results in onion bulb formation

CMT1B: Mutation in gene for p-zero

CMT2: Abnormalities in peripheral nerve axon

CMT3: Severe demyelinating, point mutation in P-zero or PMP22 genes

CMT4: Recessive demyelinating motor and sensory neuropathies

CMTX: Mutation in connexin-32 gene on X chromosome

18
Q

What are the roles of PMP22 and P-zero

A

PMP22:
- Important for the integrity of myelin sheaths
- Codes a myelin integrin protein
- Mutations cause CMTs (CMT1A and CMT3)

P-Zero
- Present in peripheral nerves, crucial protein in myelin structure
- Mutations also cause CMTs (CMT1B and CMT3)

19
Q

What does demyelination mean for the cell?

A
  • Shorter internodes and thinner myelin sheaths result in reduced conduction velocities
  • Also may result in redistribution of Na+ and K+ channels leading to conduction blocks
20
Q

What is immune-mediated polyneuropathy?

A
  • Polyneuropathy refers to neuropathy of sensory AND motor fibres
  • Patient has developed antibodies against proteins in the nodal structure (such as Caspr-connectin complexes)
21
Q

What is the potential role of myelination in circuit fine tuning?

A
  • Myelination is flexible
  • Partial myelination may contribute to learning processes by fine tuning timings of specific circuits
  • Similar concept to delay lines