Affective Behavior Shows Sex Differences in Mid-adulthood Rats Following Postnatal Immune Stimulation

Mid-adulthood represents the critical window period usually associated with the development of age-related diseases. Despite several attempts to delineate the pathological mechanisms underlying postnatal immune challenge and altered brain functions, the role of sex-dependent changes in affective behaviors of middle-aged animals requires more attention. In this study, we sought to investigate behavioral and molecular response patterns at mid-adulthood linked to early-life immune activation. Using affective behavioral test batteries, we showed that lipopolysaccharide (LPS)-induced postnatal immune challenge caused anxiety-like behaviors in both male and female Wistar rats at mid-adulthood, whereas only female rats exhibited depression-like behaviors. Our data further demonstrated a significant increase in microglial complexity and increased levels of tumor necrosis factor (TNFα), nitric oxide (NOx), and lipid peroxidation in the prefrontal cortex of female rats compared to their male counterparts and phosphate-buffered saline (PBS) littermate controls. With these results, we established significant interaction between sex differences and LPS-induced alterations in behavior and associated oxidative and immunohistochemical changes. These findings may provide an insight to better understand the neuroimmunological mechanisms of sex-dependent brain pathological manifestations occurring at mid-adulthood.