Early life stress alters microglia in ventral hippocampus and dorsal CA2 associated with anxiety-like behavior in adolescent male rats

Early-life stressors profoundly affect hippocampal development and function, with potentially detrimental consequences in adulthood. For example, adversity in early life increases the risk for the development of psychiatric disorders, including major depressive disorder (MDD), in adulthood. Pathological changes in the hippocampus are linked to altered microglial activity. Given the role of microglia in stress and development, we utilized a widely recognized rodent model to investigate how maternal separation influences inflammatory activity in stress-sensitive brain regions. Specifically, we examined the microglial morphology of Iba1-positive cells in the dorsal and ventral hippocampal subfields, the nucleus accumbens (NAc) core and shell, and the medial orbital and prelimbic areas of the prefrontal cortex. Our results reveal that the ventral hippocampus is vulnerable to early life stress and predicts anxiety-like behavior, as evidenced by increased amoeboid-shaped microglia. We also observed elevated amoeboid microglial morphology in the dorsal CA2 region. No significant changes in microglial morphology were observed in the NAc or prefrontal cortex between the stressed and non-stressed male adolescent rodents. These findings demonstrate microglial dysfunction in early life stress and support previous research linking stress, mood disorders, and inflammation. Targeting microglial activation and hippocampal neuroinflammation has the potential to develop novel therapeutics that will impact the rising global incidence of MDD and other mental illnesses.