microglia

Microglia are the resident innate immune cells of the central nervous system (CNS). Derived from primitive macrophages in the yolk sac, they migrate into the developing brain early in embryogenesis and establish a self-renewing population that persists throughout life.

In the healthy CNS, microglia have a highly ramified morphology and continuously survey their microenvironment with dynamic processes. They express markers such as Iba1 and CD11b in many species, and human microglia commonly express TMEM119 and P2RY12; colony-stimulating factor 1 receptor (CSF1R) is essential for their survival.

Functions: surveillance, debris clearance, and synaptic pruning during development via the complement cascade; rapid response to injury and infection; phagocytosis; release of cytokines (e.g., IL-1β, TNF-α), chemokines, and reactive oxygen species; interactions with neurons and astrocytes; involvement in synapse remodeling and neurogenesis. CSF1R signaling is a key regulator of microglial survival and proliferation; CX3CR1 and TREM2 are important signaling receptors that modulate their activity.

Activation and disease: Microglia can adopt multiple activation states; the M1/M2 paradigm is an oversimplification. In aging and disease they may become chronically activated, contributing to neuroinflammation. In Alzheimer's disease, microglia cluster around amyloid plaques; genetic risk variants in TREM2 and other microglial genes influence disease risk and microglial response. Microglia can both clear pathological proteins and propagate neuroinflammation. Dysfunction is implicated in multiple sclerosis, Parkinson's disease, and ALS. Research approaches include histological markers such as Iba1 and CD11b, imaging methods, and transcriptomic profiling.