Neuroinflammation Flashcards
Where do microglia arise from?
Myeloid progenitors in the yolk sac
(Mesoderm)
What are the blood counterparts of microglia?
Monocytes
What percentage of glia are microglia?
10-20%
Microglia are involved in what part of the immune system?
Innate immune system
What role do microglia play in development?
Shaping of neural circuits
Modulation of synaptic transmission
Which developmental layer do oligodendrocytes and astrocytes arise from?
Ectoderm
From what cells do oligodendrocytes arise?
Oligodendrocyte progenitor cells
Or
Neuronal stem cells
What is the function of oligodendrocytes?
Myelinate axons
Provide metabolic support to neurons
What percentage of glia are astrocytes?
50%
What is the role of astrocytes?
Neurotransmitter uptake
Maintenance of ionic homeostasis in the extracellular space
Wound healing and limiting of inflammation
Form gap junctions
Guide circuit in development
What is GFAP a marker for?
Astrocytes
What is the resting state of microglia?
Homeostatic, surveillance state - Ramified, with filopodia
How do microglia change when activated?
Lose filopodia
Amoeboid
How long do microglia last?
Almost entire life, very low turnover rate
What are the functions of microglia?
Tissue maintenance
Clearing apoptotic cells
Neuron protection
Synaptic turning
Protective
Trauma response
Pathogen response
What signals are microglia responsive to?
PAMPs, DAMPs
Pathogen/Damage Associated Molecular Patterns
Amyloid
Myelin damage (lipid signals)
Dying and stressed neurons (ATP, ADP, phosphatidylserine)
What is the microglial response?
Chemotaxis
Phagocytosis
Cytokine + chemokine release
Complement and coagulation factor release
What picks up the signal to microglia?
Pattern recognition receptors
What are the pattern recognition receptors for pathogens?
Toll like receptors
RIG receptors
MDA5 receptors
What do pro-inflammatory M1 microglia do?
Classically activated
Upregulate free radicals, hydrogen peroxide to damage pathogens
Secrete cytokines and chemokines
Defense against pathogens and tumours
However, damage healthy neurons
What do anti-inflammatory M2 microglia do?
Alternatively activated
Upregulate repair factors
Tissue remodelling/repair
Angiogenesis
What forms of systemic immune activation can prime microglia?
Acute - pathogen
Chronic CNS - dementia, depression, schizophrenia
Chronic peripheral - obesity, ageing, infections, autoimmune
What diseases are associated with oligodendrocyte dysfunction?
Mutiple Sclerosis
Multiple System Atrophy
Schizophrenia
Bipolar disorder
What diseases are associated with astrocytes dysfunction?
Alzheimer’s
ALS
SCA
Parkinson’s
Huntington’s
What diseases are associated with microglia dysfunction?
Alzheimer’s
CJD
ALS
Parkinson’s
Huntington’s
Brain injury
What feature of amyloid proteins trigger microglia?
Size and insolubility
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)
