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Neuroscience > Myelination > Flashcards

Myelination Flashcards

1
Q

what increases action potential conduction?

A

larger axon diameter

increased body temp
-> faster diffusion

myelination

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2
Q

what is myelin?

what is its purpose?

A

a specialised sheath surrounding vertebrate axons

  1. insulates axons from each other
  2. speeds up conduction via saltatory conduction between nodes of Ranvier
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3
Q

describe the differences between myelination in the PNS and CNS

A

PNS
- individual Schwann cells myelinate the axon once
(form a single myelin sheath)

CNS
- Oligodendrocytes can myelinated multiple axons or the same axon in multiple places

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4
Q

Where are Schwann cells derived from?

What is their role?

A

Neural crest

migrate + differentiate under control of peripheral axon

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5
Q

where are oligodendrocytes derived from?

what are oligodendrocytes 1 of 2 major classes of?

A

progenitors that reside in ventricular proliferating zone of neural tube

CNS glia

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6
Q

what types of cell can the O2A cell differentiate into?

what factors are required for each cells type?

A

oligodendrocyte
(low serum)

type-2 astrocyte
(BMP4 + CNTF)

(both require retinoid acid + thyroid hormone)

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7
Q

how to oligodendrocyte precursors migrate?

what molecules are required for migration?

A
  1. follow radial glia
    (outwards from ventricular zone)
  2. follow developing axon pathways
    (dorso-ventral + longitudinal)

cell adhesion molecules
(integrins, PSA-NCAM)

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8
Q

when are mature oligodendrocytes produced?

A

during myelination

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9
Q

what happens to excess oligodendrocytes?

what do progenitors compete for?

A

apoptosis

limiting amounts of mitogens + survival factors (from astrocytes + neurones)

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10
Q

which growth factors stimulate oligodendrocyte progenitor survival?

what do these ligands bind to and what does this cause?

A

neuregulin GF family NRG1-3
e.g. Glial growth factor GGF

receptors (ErbB) on undifferentiated neural crest cells that contact axons

-> sets off Raf-Raf-MAPK pathway

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11
Q

describe the different signalling between oligodendrocytes and axons

A

axons provide mitogenic signals (PDGF, neuregulin) for O2A cells

electrical activity stimulates O2A proliferation

-ve regulation of oligodendrocyte differentiation via Notch signalling

axons provide survival signals to mature oligodendrocytes

signals from neurones enhance myelin gene transcription

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12
Q

how do neural crest-derived Schwann cell progenitors migrate?

A

over the surface of the neural tube

-> then through the anterior somites

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13
Q

describe how Schwann cells myelinate axons

A
  1. identify axon
  2. Schwann cell begins to produce the myelin sheath
  3. wraps sheath around axon
  4. extrusion of material out of the myelin sheath to allow compaction around axon
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14
Q

describe the stages of Schwann cell development

A
  1. neural crest cell migrates to right location e.g. neurones, bones etc
  2. Schwann cell precursor
  3. immature Schwann cell
  4. myelinating Schwann cell
    OR
    non-myelinating Schwann cell
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15
Q

when does Schwann cell progenitor migration stop?

A

when they encounter axons

  • release neuregulins e.g. GGF expressed by motor neurones
  • > differentiation + proliferation of Schwann cell precursors
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16
Q

which 2 TF genes are important for the control of Schwann cell myelination?

A

Krox20
= zinc-finger TF
- neuregulins from axons up regulate Krox20 in Schwann cell precursors that contact them

Pax3
= paired-domain TF
- inhibits Schwann cell differentiation
-> down regulated as myelination starts

17
Q

which CAM-type molecules are important for the control of Schwann cell myelination?

what is the role of L1?

A

NCAM + L1
= expressed in Schwann cell progenitors
- down regulated after myelination starts

Myelin-associated glycoprotein (MAG) + periaxin
= might modulate interaction with axon

initiates myelination

18
Q

which CAM-type molecules are important for the control of oligodendrocyte myelination?

A

Neurofascin-155

= expressed at start of myelination

19
Q

what happens when Schwann cells mature?

why is this important?

A

lose total dependence on axon + neuregulin

autocrine survival:
NT3 (neurotrophin)
IGF2 (insulin-like GF)
PDGF-BB

enables Schwann cell survival even if axons get damaged/die
-> so can stimulate nerve regrowth

20
Q

when do Schwann cells and oligodendrocytes make myelin?

A

SC = only in present of axons

oligo = do it naturally, even in culture on their own

21
Q

what are the specialised myelin proteins?

A

P0 (SC only)
= a CAM

PLP (mostly oligo only)
= proteolipid protein

MBP (both cell types)
= myelin basic protein

MAG (both)
= myelin-associated glycoprotein

22
Q

what is the function of these specialised myelin proteins?

A

compaction/stability of myelin

PLP + P0 hold membranes together
-> help with extrusion process

23
Q

which specialised myelin protein is most abundant in the CNS myelin?

what about the PNS?

A

PLP

P0

24
Q

what are the 3 regions associated with Nodes of Ranvier?

A
  1. node - voltage
    - sensitive Na+ channels
  2. paranodal regions
    - specialised transmembrane proteins that prevent movement of Na+ and K+ channels in axon plasma membrane
  3. juxtaparanodal regions
    - K+ channels are highly concentrated
25
Q

what are the specialised proteins in the paranodal region?

A

contactin

caspr
(contactin-associated protein)

neurexin on SC interacts with contactin

26
Q

describe formation of nodal, paranodal + juxtanodal protein clusters during myelination

A

Na+ channels cluster at wide immature nodes
-> as nodes narrow + mature, Na+ channel density increases

K+ channels cluster + shift their position

  • first appear at nodes
  • > then move to paranode and then juxtaparanode as structure matures
27
Q

how does oligodendrocyte and SC binding to axons regulate Na+ and K+ clustering?

A

due to specific protein-protein contacts in the paranodal loops

28
Q

what happens in Shiverer mutant mice?

A

almost complete loss of myelination as don’t produce MBP

-> precursors cannot differentiate into oligodendrocytes

29
Q

what do mutations in the PLP gene cause?

A

hypomyelination in CNS

Neuroscience (17 decks)

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