Microglia dynamics and function in the CNS

Abstract

Microglial cells constitute the resident immune cell population of the mammalian central nervous system. One striking feature of these cells is their highly dynamic nature under both normal and pathological brain conditions. The highly branched processes of resting microglia display a constitutive mobility and undergo rapid directional movement towards sites of acute tissue disruption. Microglia can be converted by a large number of different stimuli to a chronically activated state by signaling through both purinergic and Toll-like receptor systems, among others. Recent work has uncovered some of the mechanisms underlying microglia dynamics and shed new light into the functional significance of this enigmatic member of the glial cell family.

Figure 1

Resting microglia in the mouse cerebral cortex. Microglia are labeled by EGFP expressed from the CX₃CR1 promoter. Note the highly ramified appearance of individual microglial cells, as well as the "tiled" or non-overlapping processes of microglia in the cortex. Scale bar= 100 um. Figure courtesy of Dr. Hui-tai Xu.

Figure 2

The multiple activities of microglia. Microglia exist in a highly ramified state within normal brain tissue (center). (a) The processes of microglia display constitutive motility which is dependent on ATP signaling. The functional significance of this baseline motility remains unclear. (b) Microglial processes are rapidly recruited to sites of CNS tissue damage. The signals responsible for this recruitment include ATP and NO, etc. (c) Signaling though many pathways including those utilizing purinergic (P1, P2X, and P2Y) and toll-like receptors (TLRs) leads to a state of chronic microglial activation. As a result, microglia may release soluble factors that act in a trophic, protective, or anti-inflammatory manner on surrounding CNS cells.