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Neuroscience and Mental Health > Oligodendrocytes > Flashcards

Oligodendrocytes Flashcards

1
Q

Describe the origin of oligodendrocyte precursor cells (OPCs)

A

neuroepithelium -> CNS -> neural tube fusion -> SVZ cells -> OPCs

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2
Q

What arises from OPCs?

A
  • oligodendrocytes
  • astrocytes

(in culture: both
in body: more oligodendrocyte)

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3
Q

Key marker of oligodendrocyte precursors?

A

PDGF-alpha receptor

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4
Q

Relationship between PDGF-ar and O-2A cells?

A

Type 1 astrocytes secrete PDGF (PDGF-AA and BB), which is received by O-2A cells (via PDGFalphaalpha receptor)

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5
Q

Where does PDGFaR cell foci first appear?

A

Ventral spinal cord (in ventricular zone)

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6
Q

What is Olig2?

A

General marker for oligodendrocyte lineage. A basic helix-loop-helix transcription factor

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7
Q

Role of the notochord w/ oligodendrocytes?

A

Notochord is essential for OPCs and motor neurons (as they share the same progenitors)

NB: mouse lacking notochord/floor plate -> no OPCs or motor neurons

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8
Q

How is there cell type specification for oligodendrocytes?

A

Morphogenic gradients (SHH/BMP4) -> these activate diff t.factors depending on diff morphogen conc.s -> specifies cell types

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9
Q

Describe mechanism of opposing morphogenic gradients for oligodendrocytes

A

Notochord (floor plate) produces SHH (diffuses up like a hedgehog spine)
Ectoderm (roof plate) produces BMP4 (diffuses downward)

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10
Q

Role of Olig1?

A

Not essential for OPC production BUT required for maturation (marker = MBP) into oligodendrocytes

KO: OPCs present + contact but don’t myelinate axons

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11
Q

Role of Olig2?

A

Required for oligodendrocytes in spinal cord

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12
Q

Effect of SHH?

A

Promotes oligodendrocyte development

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13
Q

Effect of (bone morphogenic protein 4) BMP4?

A

Inhibits oligodendrocyte development

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14
Q

Effect of SHH and BMP4 on astrocytes?

A

none

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15
Q

How do OPCs move to target site?

A

Pushed along axons by Netrin-1 and Semma3a

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16
Q

Factors involved in oligodendrocyte proliferation?

A

PDGF
FGF2
Neuregulin beta-1

17
Q

Effect of PDGF on oligodendrocytes?

A

Increased proliferation (dose-dose dependent)

Once PDGF decreases -> differentiation occurs

18
Q

Effect of FGF2 on oligodendrocytes?

A
  • Increased proliferation
  • Increased migration
  • Decreased differentiation
19
Q

Effect of neuregulin beta-1 on oligodendrocytes?

A
  • Increased proliferation

- increased differentiation

20
Q

Factors involved in oligodendrocyte differentiation?

A
  • YY1
  • Myelin Gene Regulatory Factor (MRF)
  • Olig1/2 (activators)
  • Sox5 (inhibitor)
21
Q

Effect of Ying Yan 1 (YY1)

A

Represses transcriptional inhibitors of myelin gene (inhibits the inhibitors)

22
Q

What is MRF and outcome of its KO?

A

CNS-specific nuclear protein expressed only in post-mitotic oligogendrocytes

KO: decreased myelin gene exp -> No CNS myelin -> ataxia

23
Q

Relevance of axonal contact?

A

Required for oligodendrocyte survival (without input, cell dies by apoptosis)

[prevents overproduced cell survival]

24
Q

How oligodendrocytes initiate axonal contact?

A

Developing oligodendrocytes extend many radial processes to contact axons ->

  • those that do not contact are withdrawn
  • if no contact with any axons -> apoptosis
  • axonal contact -> myelination
25
Q

How do oligodendrocyte processes locate axons?

A

Axons express survival signals e.g. NCAM.

NCAM binds to same protein on olig process -> Ig-Ig interaction -> conform change -> cell survival signal

26
Q

Overview of mechanisms that trigger myelination

A
  • electrical activity in axon
  • NCAM on axon stimulates survival
  • inhib molecules downregulation (PSA-NCAM)
  • axo-glial signals promote myelination
27
Q

How electrical activity in axon triggers myelination?

A

Electrical activity -> ATP release -> astrocytes secrete LIF -> LIF promotes olig survival

28
Q

Describe the physical process of myelination

A

Oligodendrocyte process contacts axon and leading process tucks under previously deposited membrane

Cytoplasm restricted to tighten this structure (end loops adhere to axon membrane)

Wrapping and lateral extension

29
Q

[during myelination]

How do end loops of oligodendrocyte adhere to axonal membrane

A

NF155 and Caspr-1

30
Q

How are nodes of Ranvier formed?

A

[triggered by myelination]

Clustering of Na+ channels -> STOP signal -> forms node of Ranvier

Myelin stops the current leakage by segregating ion channels (nodal Na+, paranodal K+)

31
Q

Myelin structure: what are the dark lines and lighter lines composed of?

A

Dark lines: compacted intracellular faces of membrane (protein rich)

Lighter lines: compacted extracellular faces of the membrane

32
Q

How is myelin remodelling possible in an adult CNS?

A

OPCs continue to proliferate and generage myelinating oligodendrocytes

[role in learning]

Neuroscience and Mental Health (65 decks)

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