Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing child-hood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic -pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glu-tamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hip-pocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV -positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

Automated summary

It has been reported that early life stressful events can influence adult behavior and are associated with various psychiatric disorders. Maternal separation (MS) in animals is a well-known model for studying childhood stress and depression. This study investigated the effects of MS on anxiety and aggression-like behavior as well as the number of GABAergic neurons in the hippocampus. The results showed that MS led to increased anxiety and aggression in behavior tests and an increase in GAD67 and PV positive neurons in different regions of the hippocampus. These changes were accompanied by an increase in corticosterone, suggesting involvement of the HPA axis. Overall, MS alters anxiety and aggression levels, possibly through changes in hippocampal cytoarchitecture and HPA axis function.