Of the roughly 70% of cells in the central nervous system (CNS) that are glia, appromixately 5-10% are microglial cells. Microglial cells are derived from peripheral myeloid progenitor cells that enter the CNS during embryonic development. Though ubiquitous in the CNS, microglial cell densities vary by region. They function to provide structural and trophic support to neurons and serve as the resident immune-competent cells of the CNS, tasked with:
- detection of infections and injuries
- protection of healthy tissues
- elimination of disturbances
- restoration of homeostatic conditions
Normally, microglial morphology is characterized by small soma with many thin, branded processes. Microglial processes come in contact with neurons, endothelial cells and astrocytes but not other microglial cells. In fact, each cell appears to be responsible for a distinct territory, within which it contantly samples the extracellular microenvironment by sweeping its processes through the tissue without disrupting neuronal connectivity.
Microglial cells have a very low threshold for activation and can be activated by a wide vavriety of stimuli. Once activated, they undergo morphological and phyiological changes and they mobilize and proliferate. Activated cells display enlarged soma with shorter processes or even amoeba-like shapes and drmatically altered gene expression profiles. They home to injured areas, perform phagocytic and antigen presentation functions, and re-enter the cell cycle to increase their number. As microglial cells are not electrically coupled with other cells, they act solely via the release of diffusible mediators to communicate with neighboring cells in a paracrine fashion. Microglial phenotypes are extremely plastic. The process of microglial activation is neither an "all-or-none" committment, nor a linear path, which allows for creation of a wide range of activated phenotypes to achieve very graded responses to real or perceived threats to the CNS. Taken together with evidence of microglial populations haven already "built-in" heterogeneity and the possibilitiy that when individual cells are activated once, they may respond differently when activated again through potentially long-lasting epigenetic mechanismsm, the picture of microglial activities in the CNS becomes extremely complex.