Maternal separation leads to regional hippocampal microglial activation and alters the behavior in the adolescence in a sex-specific manner

Early life adversities during childhood (such as maltreatment, abuse, neglect, or parental deprivation) may increase the vulnerability to cognitive disturbances and emotional disorders in both, adolescence and adulthood. Maternal separation (MS) is a widely used model to study stress-related changes in brain and behavior in rodents. In this study, we investigated the effect of MS (postnatal day 2–14, 3 ​h/day) in both, female and male adolescent mice. Specifically, we evaluated (i) the spatial working memory, anxiety and depressive-like behavior, (ii) the hippocampal synaptic gene expression, and (iii) the hippocampal neuroinflammatory response. Our results show that MS significantly increased depressive-like behavior in adolescent female mice and altered the spatial memory in adolescent male mice. In addition, MS led to decreased expression of genes related to synaptic function (5ht6r, Synaptophysin, and Cox-2) and induced an exacerbated microglial activation in dentate gyrus (DG), CA1, and CA3. However, while the levels of hippocampal inflammatory cytokines were not modified by MS, they did follow a sex-specific expression in adolescent mice. Taken together, our results suggest that MS induces long-term changes in hippocampal microglia and synaptic gene expression, alters the spatial memory, and induces depressive-like behavior in the adolescent mice, in a sex-specific manner.