The formative role of microglia in stress-induced synaptic deficits and associated behavioral consequences.

Psychological stress can precipitate depression, and emerging preclinical data suggest a link between stress-induced alterations in microglia function and development of depressive-like behaviors. Microglia are highly dynamic, and play an integral role in maintaining neuronal homeostasis and synaptic plasticity. In this capacity, microglial dysfunction represents a compelling avenue through which stress might disrupt neuronal integrity and induce psychopathology. This review examines preclinical and clinical postmortem findings that indicate microglia-neuron interactions contribute to stress-induced synaptic deficits and associated behavioral and cognitive consequences. We focus on pathways that are implicated in microglia-mediated neuronal remodeling, including CSF1-CSF1R, CX3CL1-CX3CR1, and CD11b (CR3)-C3, as well as purinergic signaling via P2RX7 and P2RY12. We also highlight sex differences in stress effects on microglia, and the potential for microglia in the development of sex-specific treatments for depressive disorders.