Effects of Early Stress Exposure on Anxiety-like Behavior and Expression in Rats.

Exposure to stress during early and late childhood can lead to long-lasting neurobiological and behavioral impairments. Although sensitive periods for stress exposure are well established, less is known about the trajectory of induced alterations throughout development. In this study, we investigated the impact of maternal separation (MS), social isolation, and their combination on anxiety-like behavior and gene expression across developmental stages. Sprague Dawley rats were exposed to one or both stressors and later assessed for anxiety-like behavior in juvenility, adolescence, and adulthood. mRNA levels of , a gene linked to early-life stress and depression, were measured in the medial prefrontal cortex to assess developmental changes. The results showed that MS had age- and sex-dependent effects on anxiety-like behavior. Juveniles exhibited less anxiety after MS, while adolescents showed more pronounced behavioral changes following social isolation. No behavioral changes were observed in adults. Males exhibited greater anxiety-like behavior than females in adolescence and adulthood, but not in juvenility. Female adults exposed to both MS and social isolation had significantly lower expression compared to controls. These findings highlight the dynamic effects of early stress across the lifespan, underscoring the critical role of adolescence and differential stress susceptibility by age and sex.