Microglial Physiology: Unique Stimuli, Specialized Responses

TLDR

Microglia are CNS macrophages that maintain a distinct phenotype through neuronal and astrocytic signals and the blood‑brain barrier, continuously survey their environment, and rapidly change morphology and surface markers in response to disturbances. The authors argue that the term “activated microglia” must be qualified to reflect distinct activation states, and that targeting their effector functions could alter the course of various neurological diseases. Recent evidence shows that microglia possess diverse effector functions comparable to macrophages in other tissues.

Abstract

Microglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases.