Neuroinflammation Flashcards

1
Q

Where do microglia arise from?

A

Myeloid progenitors in the yolk sac
(Mesoderm)

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2
Q

What are the blood counterparts of microglia?

A

Monocytes

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3
Q

What percentage of glia are microglia?

A

10-20%

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4
Q

Microglia are involved in what part of the immune system?

A

Innate immune system

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5
Q

What role do microglia play in development?

A

Shaping of neural circuits
Modulation of synaptic transmission

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6
Q

Which developmental layer do oligodendrocytes and astrocytes arise from?

A

Ectoderm

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7
Q

From what cells do oligodendrocytes arise?

A

Oligodendrocyte progenitor cells
Or
Neuronal stem cells

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8
Q

What is the function of oligodendrocytes?

A

Myelinate axons
Provide metabolic support to neurons

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9
Q

What percentage of glia are astrocytes?

A

50%

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10
Q

What is the role of astrocytes?

A

Neurotransmitter uptake
Maintenance of ionic homeostasis in the extracellular space
Wound healing and limiting of inflammation
Form gap junctions
Guide circuit in development

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11
Q

What is GFAP a marker for?

A

Astrocytes

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12
Q

What is the resting state of microglia?

A

Homeostatic, surveillance state - Ramified, with filopodia

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13
Q

How do microglia change when activated?

A

Lose filopodia
Amoeboid

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14
Q

How long do microglia last?

A

Almost entire life, very low turnover rate

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15
Q

What are the functions of microglia?

A

Tissue maintenance
Clearing apoptotic cells
Neuron protection
Synaptic turning

Protective
Trauma response
Pathogen response

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16
Q

What signals are microglia responsive to?

A

PAMPs, DAMPs

Pathogen/Damage Associated Molecular Patterns

Amyloid

Myelin damage (lipid signals)

Dying and stressed neurons (ATP, ADP, phosphatidylserine)

17
Q

What is the microglial response?

A

Chemotaxis
Phagocytosis
Cytokine + chemokine release
Complement and coagulation factor release

18
Q

What picks up the signal to microglia?

A

Pattern recognition receptors

19
Q

What are the pattern recognition receptors for pathogens?

A

Toll like receptors
RIG receptors
MDA5 receptors

20
Q

What do pro-inflammatory M1 microglia do?

A

Classically activated

Upregulate free radicals, hydrogen peroxide to damage pathogens
Secrete cytokines and chemokines

Defense against pathogens and tumours

However, damage healthy neurons

21
Q

What do anti-inflammatory M2 microglia do?

A

Alternatively activated

Upregulate repair factors

Tissue remodelling/repair
Angiogenesis

22
Q

What forms of systemic immune activation can prime microglia?

A

Acute - pathogen
Chronic CNS - dementia, depression, schizophrenia
Chronic peripheral - obesity, ageing, infections, autoimmune

23
Q

What diseases are associated with oligodendrocyte dysfunction?

A

Mutiple Sclerosis
Multiple System Atrophy
Schizophrenia
Bipolar disorder

24
Q

What diseases are associated with astrocytes dysfunction?

A

Alzheimer’s
ALS
SCA
Parkinson’s
Huntington’s

25
What diseases are associated with microglia dysfunction?
Alzheimer’s CJD ALS Parkinson’s Huntington’s Brain injury
26
What feature of amyloid proteins trigger microglia?
Size and insolubility
27
What evidence is there that neuroinflammation has a role in Alzheimer’s Disease?
Activated microglia clustering around plaques Immune associated genes found in GWAS Evidence of NSAIDs being protective against AD Rare microglial genes in AD (TREM2)