MICROGLIAL BIOLOGY
Microglial cells are mesenchymal
cells derived from yolk sac that come to reside in the CNS. They are a unique
resident population with the capacity for self-renewal. Microglia provide
constant surveillance of the local microenvironment, moving back and forth up
to 1.5 µm/min. Microglial processes can grow and shrink up to 2-3 µm/min. They
have a territory 15-30 µm wide, with little overlap with each other. Resting
microglia have soma of 5-6 µm diameter, and activated microglia are ameboid in
appearance, with soma of approximately 10 µm diameter.
Microglia can carry out
phagocytosis of debris and apoptotic cells, remodel and remove synapses in
developing and adult CNS, and respond to injury or pathogens. Microglia have
receptors for multiple types of stimuli, such as ATP (indicator of local
damage), toll-like receptors (TLRs) that respond to molecules released from
dying cells (DAMPS: damage-associated molecular patterns) or pathogens (PAMPS:
pathogen associated molecular patterns) such as LPS on gram-negative bacteria,
or double-stranded RNA in viruses.
Reactive microglia produce reactive
oxygen species (ROS), reactive nitrogen species (RNS, such as NO),
proinflammatory cytokines (IL-1β, IL-6, TNF-α), matrix metalloproteinases
(MMPs), and neurotrophic factors (such as NGF, TGF-β, neurotrophin 4/5, GDNF,
FGF). Such signal molecules from activated microglia can affect neurons and
astrocytes, inducing dysfunction.