Postweaning swimming exercise attenuates maternal sleep deprivation-induced aggressive behavior in offspring mice.

Sleep deprivation (SD) has become increasingly prevalent, drawing growing attention to its associated behavioral alterations and health consequences. Among pregnant women, SD tends to worsen with advancing gestational age. However, its effects on offspring aggression remain underexplored. This study examined how late gestational SD affected aggressive behavior in adolescent offspring mice and evaluated postweaning swimming exercise in warm water as a potential intervention against adverse outcomes induced by early life stress in offspring. Results showed that late gestational SD significantly increased aggressive behavior, decreased the serum level of CD3+CD4+ T cells and increased serum IL-6 level of adolescent male offspring, which were reversed by postweaning swimming exercise. Furthermore, late gestational SD increased c-Fos expression levels in the ventromedial hypothalamic nucleus, anterior hypothalamic nucleus, periaqueductal gray and paraventricular thalamus (PVT) in adolescent male offspring, and postweaning swimming exercise could also reverse this change. Microinjection of recombinant IL-6 or a neutralizing anti-IL-6 antibody directly into the PVT demonstrated that elevated IL-6 levels within the PVT increased individual aggressive behavior, which was consistent with the late gestational SD-induced increase in IL-6 content in the PVT. Our primary data indicate that late gestational SD may trigger aggressive behavior in adolescent offspring through IL-6-mediated changes in immune markers and neural circuit abnormalities, and postweaning swimming exercise has protective effects. These findings offer fresh insight into the neuroimmune regulatory mechanisms underlying aggressive behavior, which highlight the importance of exercise and anti-inflammatory strategies as effective approaches to mitigating the adverse effects of early life stress on aggression.