Neuroinflammation

Question 1

Where do microglia arise from?

Answer 1

Myeloid progenitors in the yolk sac
(Mesoderm)

Question 2

What are the blood counterparts of microglia?

Answer 2

Monocytes

Question 3

What percentage of glia are microglia?

Answer 3

10-20%

Question 4

Microglia are involved in what part of the immune system?

Answer 4

Innate immune system

Question 5

What role do microglia play in development?

Answer 5

Shaping of neural circuits
Modulation of synaptic transmission

Question 6

Which developmental layer do oligodendrocytes and astrocytes arise from?

Answer 6

Ectoderm

Question 7

From what cells do oligodendrocytes arise?

Answer 7

Oligodendrocyte progenitor cells
Or
Neuronal stem cells

Question 8

What is the function of oligodendrocytes?

Answer 8

Myelinate axons
Provide metabolic support to neurons

Question 9

What percentage of glia are astrocytes?

Answer 9

50%

Question 10

What is the role of astrocytes?

Answer 10

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

Question 11

What is GFAP a marker for?

Answer 11

Astrocytes

Question 12

What is the resting state of microglia?

Answer 12

Homeostatic, surveillance state - Ramified, with filopodia

Question 13

How do microglia change when activated?

Answer 13

Lose filopodia
Amoeboid

Question 14

How long do microglia last?

Answer 14

Almost entire life, very low turnover rate

Question 15

What are the functions of microglia?

Answer 15

Tissue maintenance
Clearing apoptotic cells
Neuron protection
Synaptic turning

Protective
Trauma response
Pathogen response

Question 16

What signals are microglia responsive to?

Answer 16

PAMPs, DAMPs

Pathogen/Damage Associated Molecular Patterns

Amyloid

Myelin damage (lipid signals)

Dying and stressed neurons (ATP, ADP, phosphatidylserine)

Question 17

What is the microglial response?

Answer 17

Chemotaxis
Phagocytosis
Cytokine + chemokine release
Complement and coagulation factor release

Question 18

What picks up the signal to microglia?

Answer 18

Pattern recognition receptors

Question 19

What are the pattern recognition receptors for pathogens?

Answer 19

Toll like receptors
RIG receptors
MDA5 receptors

Question 20

What do pro-inflammatory M1 microglia do?

Answer 20

Classically activated

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

Defense against pathogens and tumours

However, damage healthy neurons

Question 21

What do anti-inflammatory M2 microglia do?

Answer 21

Alternatively activated

Upregulate repair factors

Tissue remodelling/repair
Angiogenesis

Question 22

What forms of systemic immune activation can prime microglia?

Answer 22

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

Question 23

What diseases are associated with oligodendrocyte dysfunction?

Answer 23

Mutiple Sclerosis
Multiple System Atrophy
Schizophrenia
Bipolar disorder

Question 24

What diseases are associated with astrocytes dysfunction?

Answer 24

Alzheimer’s
ALS
SCA
Parkinson’s
Huntington’s

Question 25

What diseases are associated with microglia dysfunction?

Answer 25

Alzheimer’s
CJD
ALS
Parkinson’s
Huntington’s
Brain injury

Question 26

What feature of amyloid proteins trigger microglia?

Answer 26

Size and insolubility

Question 27

What evidence is there that neuroinflammation has a role in Alzheimer’s Disease?

Answer 27

Activated microglia clustering around plaques
Immune associated genes found in GWAS
Evidence of NSAIDs being protective against AD
Rare microglial genes in AD (TREM2)