Role of Microglia in Neural Systems Flashcards
Name 4 CNS glia
Astrocytes
Microglia
Oligodendrocytes
NG2 cells
What are the roles of astrocytes?
Induce widespread neuronal excitation - modulate CNS activity
Cause blood vessel dilation
What is the role of oligodendrocytes?
Adaptive myelination - in response to neuronal activity - into adult life - required in corpus callosum for motor learning
What are the roles of microglia?
Resident CNS immune cells
Regulate neuronal plasticity - by influencing neuronal activity
Synaptic pruning
Phagocytosis
Describe the morphology of non-activated microglia
Small cell body
Long ramified processes
Describe the morphology of activated microglia
Ameboid shape
Processes move towards lesion
What is a microdomain?
Space occupied by microglial cell - forms grid-like arrangement
How do microglia perform synaptic pruning in development?
Engulf axons and dendritic spines
What is a complement protein and where are they expressed?
‘Eat me’ signals
On unnecessary neuronal structures - e.g. immature synapses in developing CNS
Where are complement receptors expressed?
Only on microglia
Name 2 complement proteins, the signalling pathway they activate, and the resulting action of microglia
C3, C1q
Activates C3-C3R pathway
Microglia phagocytose synapse
How do microglia influence neuronal activity?
Processes directed to highly active neurons - by neuronally-released signalling molecules
Processes engage with soma of highly-active neurons
Decreases spontaneous and evoked firing
Describe the process of programmed cell death. When does this occur?
During development
Microglia drive PCD via complement signalling
Processes attracted to relevant neuron
Project phagocytic cup - engulfs neurons
Describe the process of synapse maturation
Synapse strengthened by CX3CR1-dependent mechanism - involves microglia
Synapse maturation - NMDAR subunit changes and AMPAR insertion
What are the aberrant functions of microglia?
Excessive synaptic pruning - can cause cognitive dysfunction
Inflammatory cytokine release - promote neurotoxicity
What is the effect of an early challenge to microglia in the developing CNS?
Primes microglia - no immediate effect on CNS
More susceptible to later challenges - delayed effect - increases later-life disease risk
What is necessary for toxic AB effects on synapses?
C1q
How has ASD been linked to microglia?
Deficit in microglial complement-mediated pruning - due to decreased C3 expression
CX3CR1-deficient mice have increased immature synapse density in cortex - lack of strengthening and maturation
Which locus and type of genes have GWAS linked to SCZ?
MHC locus
C4 complement genes
What are the effects of increased C4a expression?
Increased SCZ risk
Increased microglial activity - increased synaptic pruning
How is synaptic density changed in SCZ patients?
Reduced
Where do microglia accumulate in neuropathic pain?
Around terminals of damaged inputs in dorsal spinal cord - in synapse between damaged primary afferent neuron and DRG neuron
Which molecule is released by injured sensory neurons into the dorsal horn?
CSF1
What is the effect of CSF1?
Triggers microglial proliferation
CSF1R-expressing microglia adopt reactive phenotype - involves P2X4R upregulation
P2X4R activation stimulates BDNF release - onto neurons - activates neruonal trkB
TrkB downregulates KCC2 - causes disinhibition of nociceptive output neurons to brain
