Stress, Microglial Activation, and Mental Disorders

Abstract

Microglia play a major role in immune response in the brain. Recent progress in studies for microglia suggests that stress causes morphological alterations in microglia and affects microglial humoral release and phagocytosis. In this review, we present a molecular mechanism by which stress impacts microglia. Then, we describe current findings for the involvement of microglia in stress-related mental disorders including posttraumatic stress disorder (PTSD), depression, and pain enhancement. We focus on preclinical and clinical studies. Preclinical PTSD studies using animal models with fear memory dysregulation show neuroinflammation by microglia and altered microglial phagocytosis, two imaging studies and a postmortem study assessing neuroinflammation in PTSD patients show contradictory results. Imaging studies suggest neuroinflammation in depressed patients, postmortem studies show no microglial inflammatory changes in non-suicidal depressed patients. Although it has been established that microglia in the spinal cord play a pivotal role in chronic neuropathic pain, several preclinical studies suggest microglia also participate in stress-induced pain. A clinical study with induced microglia-like (iMG) cells and an imaging study indicate neuroinflammation by microglia in fibromyalgia patients. We believe that progress in interactive research between humans and animals elucidates the role of microglia in the pathophysiology of stress-related mental disorders.