Interaction between neurons and microglia in healthy and disease states

Interactions between neurons and microglia are essential for various brain functions under both healthy and pathological states. Microglia have classical functions as immune cells, causing cerebral inflammation, whereas their reparative roles after acute cerebral inflammation have recently attracted attention. In the healthy brain state, microglia contribute to homeostasis and brain tissue development. Microglia regulate neuronal activity by responding to molecules derived from neurons and eliminating excess synapses to achieve normal brain development and maintain a homeostatic brain environment. Microglia are also involved in neuronal information processing, such as learning and memory, by modulating synaptic remodeling and neurogenesis. In contrast, aging alters brain homeostasis and increases vulnerability to neurodegenerative pathologies through changes in interactions between neurons and microglia. Microglia exert diverse functions in neurological and psychiatric diseases. Microglia are responsible for rapid inflammatory responses by receiving abnormal signals from injured brain cells. Excess neuroinflammation mediated by disease-associated microglia exacerbates the pathology of central nervous system (CNS) diseases. Recent studies have also revealed the roles of microglia in improving pathologies through the phagocytosis of neurotoxic proteins and damaged or excess synapses. This review highlights the interaction between neurons and microglia in both healthy and pathological brain states. Understanding these interactions could lead to the development of therapeutic strategies by regulating the pathologies underlying various CNS disorders.