Neuroimmunometabolism: how metabolism orchestrates immune response in healthy and diseased brain

Neuroimmunometabolism describes how neuroimmune cells, such as microglia, adapt their intracellular metabolic pathways to alter their immune functions in the central nervous system (CNS). Emerging evidence indicates that neurons also orchestrate the microglia-mediated immune response through neuro-immune cross talk, perhaps through metabolic signaling. However, little is known about how the brain's metabolic microenvironment and microglial intracellular metabolism orchestrate the neuroimmune response in healthy and diseased brains. This review addresses the balance of immunometabolic substrates in healthy and diseased brains, their metabolism by brain-resident microglia, and the potential impact of metabolic dysregulation of these substrates on the neuroimmune response and pathophysiology of psychiatric disorders. This review also suggests metabolic reprogramming of microglia as a preventive strategy for the management of neuroinflammation-related brain disorders, including psychiatric diseases.