Microglia as Dynamic Cellular Mediators of Brain Function

Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more complex roles in normal brain development and in the context of disease. In health, microglia influence neural progenitor fate decisions, astrocyte activation, neuronal homeostasis, and synaptogenesis. In the setting of brain disease, including autism, brain tumors, and neurodegenerative disorders, microglia undergo substantial morphological, molecular, and functional changes, which establish new biological states relevant to disease pathogenesis and progression. In this review, we discuss the function of microglia in health and disease and outline a conceptual framework for elucidating their specific contributions to nervous system pathobiology. Microglia integrate genomic and genetic alterations, as well as local microenvironment and systemic signals, to establish new functional states that modify neurologic diseases.Transcriptional profiling has revealed several different microglia populations/states with distinct functional properties.Understanding the molecular mechanisms that govern microglia adaptation and plasticity may lead to the development of targeted therapies for a broad range of neurologic disorders.