Supporting microglial niches for therapeutic benefit in psychiatric disorders

Abstract

Inflammation is an essential tissue response to injury, stress, or infection resulting in debris and/or pathogen clearance intended to promote healing and recovery. Due to the status as an immune 'privileged' tissue, microglia serve as endogenous regulators of inflammation in the central nervous system, but maintain communication with peripheral immune system to enable recruitment of peripheral immune cells in case of injury or infection. While microglia retain the functional capacity for a full range of inflammatory functions - microglia express a range of pattern-recognition receptors and function as innate immune cells, carry out phagocytosis of pathogens, and act as antigen presenting cells - in the healthy central nervous system (CNS) these functions are rarely engaged. Subsequently microglia are being recognized to occupy an increasing number of homeostatic niches, and in many cases have adopted immune or inflammatory mechanisms to carry out these niche functions absent immune activation. These sterile inflammatory functions are challenging long-held views of the role of inflammation in the central nervous system while simultaneously expanding the potential for the development of truly novel therapeutic interventions for a range of neuroinflammatory, neurodegenerative, and neuropsychiatric disorders. In the present review we discuss recent preclinical evidence for conserved niche functions for microglia whose disruption may causally contribute to various psychiatric disorders, and prospective targets for restoring disrupted niches.