Postweaning intermittent sleep deprivation enhances defensive attack in adult female mice via the microbiota-gut-brain axis

Sleep is one of the most important physiological activities in life and promotes the growth and development of an individual. In modern society, sleep deprivation (SD), especially among adolescents, has become a common phenomenon. However, long-term SD severely affected adolescents' neurodevelopment leading to abnormal behavioral phenotypes. Clinical studies indicated that sleep problems caused increased aggressive behavior in adolescents. Aggressive behavior was subordinate to social behaviors, in which defensive attack was often the last line for survival. Meanwhile, increasing studies shown that gut microbiota regulated social behaviors by affecting specific brain regions via the gut-brain axis. However, whether postweaning intermittent SD is related to defensive attack in adulthood, and if so, whether it is mediated by the microbiota-gut-brain axis are still elusive. Combined with microbial sequencing and hippocampal metabolomics, the present study mainly investigated the long-term effects of postweaning intermittent SD on defensive attack in adult mice. Our study demonstrated that postweaning intermittent SD enhanced defensive attack and impaired long-term memory formation in adult female mice. Moreover, microbial sequencing and LC-MS analysis showed that postweaning intermittent SD altered the gut microbial composition and the hippocampal metabolic profile in female mice, respectively. Our attention has been drawn to the neuroactive ligand-receptor interaction pathway and related metabolites. In conclusion, our findings provide a new perspective on the relationship of early-life SD and defensive attack in adulthood, and also highlight the importance of sleep in early-life, especially in females.