Sex-dependent and long-lasting effects of adolescent sleep deprivation on social behaviors in adult mice.

Increasing evidence indicates that sleep deprivation (SD) can exert multiple negative effects on neuronal circuits, resulting in memory impairment, depression, and anxiety, among other consequences. The long-term effects of SD during early life on behavioral phenotypes in adulthood are still poorly understood. In this study, we investigated the long-lasting effects of SD in adolescence on social behaviors, including empathic ability and social dominance, and the role of the gut microbiota in these processes, using a series of behavioral paradigms in mice combined with 16S rRNA gene pyrosequencing. Behavioral assay results showed that SD in adolescence significantly reduced the frequency of licking, the total time spent licking, and the time spent sniffing during the emotional contagion test in male mice, effects that were not observed in female mice. These findings indicated that SD in adolescence exerts long-term, negative effects on empathic ability in mice and that this effect is sex-dependent. In contrast, SD in adolescence had no significant effect on locomotor activities, social dominance but decreased social interaction in male mice in adulthood. Meanwhile, 16S rRNA gene pyrosequencing results showed that gut microbial richness and diversity were significantly altered in adult male mice subjected to SD in adolescence. Our data provide direct evidence that SD in youth can induce alterations in empathic ability in adult male mice, which may be associated with changes in the gut microbiota. These findings highlight the long-lasting effects of sleep loss in adolescence on social behaviors in adulthood and the role played by the brain-gut axis.