Astrocytes and Microglia: In Sickness and in Health

Astrocytes and microglia perform complementary roles during brain development and physiology. Among the best studied of these are their roles in supporting synapse development and responding to neuronal signals. Astrocytes and microglia may coordinate their supportive functions in other, less studied physiologic processes, including myelination, blood–brain barrier regulation, and angiogenesis. In response to injury, inflammation, and degenerative diseases, context-specific signals can shape both astrocyte and microglial responses. This type of synchrony in the astrocytic–microglial unit has been demonstrated in mouse models of Alzheimer’s disease, multiple sclerosis, and encephalitis. Molecular mechanisms that regulate astrocyte–microglia communication include direct signaling through cytokines and other molecules, as well as distinct but coordinated responses to shared environmental signals such as purines and norepinephrine. In pathology, blood-derived factors help to synchronize the astrocyte–microglia unit. Healthy central nervous system (CNS) development and function require an intricate and balanced bidirectional communication between neurons and glia cells. In this review, we discuss the complementary roles of astrocytes and microglia in building the brain, including in the formation and refinement of synapses. We discuss recent evidence demonstrating how these interactions are coordinated in the transition from healthy physiology towards disease and discuss known and potential molecular mechanisms that mediate this cellular crosstalk. Healthy central nervous system (CNS) development and function require an intricate and balanced bidirectional communication between neurons and glia cells. In this review, we discuss the complementary roles of astrocytes and microglia in building the brain, including in the formation and refinement of synapses. We discuss recent evidence demonstrating how these interactions are coordinated in the transition from healthy physiology towards disease and discuss known and potential molecular mechanisms that mediate this cellular crosstalk.