Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

• Published in: PloS one Vol. 12; no. 12; p. e0187631
• Main Authors: Bollinger, Justin L, Collins, Kaitlyn E, Patel, Rushi, Wellman, Cara L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2017; Public Library of Science (PLoS)
• Subjects: Activation; Amygdala; Animal behavior; Animals; Anxiety; Behavioral plasticity; Biology and Life Sciences; Brain; Brain - metabolism; CD200 antigen; CD40 antigen; Cell interactions; Cellular stress response; Cognitive ability; CX3CR1 protein; Dendritic plasticity; Female; Females; Gender aspects; Gender differences; Gene expression; Immune system; Influence; Limbic System - metabolism; Male; Males; Medicine and Health Sciences; Mental depression; Mental disorders; Microglia; Microglia - metabolism; Morphology; Neuronal-glial interactions; Nitric-oxide synthase; Physiological aspects; Polymerase Chain Reaction; Prefrontal cortex; Psychological aspects; Punches; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Residential density; Rodents; Sex; Sex differences; Sexual behavior; Social Sciences; Stress; Stress (Psychology); Stress, Psychological; Stresses; Structure-function relationships; Synaptic plasticity; Women; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187631

Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress-induced dendritic remodeling across OFC, BLA, and DHC. Together, these data suggest the potential for microglia-mediated sex differences in stress effects on neural structure, function, and behavior.