Postweaning stress affects behavior, brain and gut microbiota of adolescent mice in a sex-dependent manner

• Published in: Neuropharmacology 2024-05, Vol.248, p.109869-109869, Article 109869
• Main Authors: Yin, Xueyong, Zhao, Ye, Wang, Shuang, Feng, Hao, He, Xinyue, Li, Xincheng, Liu, Xiaoyu, Lu, Hengtai, Wen, Di, Shi, Yun, Shi, Haishui
• Format: Article
• Language: English
• Subjects: Defensive aggression; Dendritic spine density; Early-life stress; Gut microbiota; Postweaning
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2024.109869

Aggression is an instinctive behavior that has been reported to be influenced by early-life stress. However, the potential effects of acute stress during the postweaning period, a key stage for brain development, on defensive aggression and the associated mechanism remain poorly understood. In the present study, aggressive behaviors were evaluated in adolescent mice exposed to postweaning stress. Serum corticosterone and testosterone levels, neural dendritic spine density, and gut microbiota composition were determined to identify the underlying mechanism. Behavioral analysis showed that postweaning stress reduced locomotor activity in mice and decreased defensive aggression in male mice. ELISA results showed that postweaning stress reduced serum testosterone levels in female mice. Golgi staining analysis demonstrated that postweaning stress decreased neural dendritic spine density in the medial prefrontal cortex of male mice. 16S rRNA sequencing results indicated that postweaning stress altered the composition of the gut microbiota in male mice. Combined, these results suggested that postweaning stress alters defensive aggression in male mice, which may be due to changes in neuronal structure as well as gut microbiota composition. Our findings highlight the long-lasting and sex-dependent effects of early-life experience on behaviors. •Postweaning stress reduced defensive aggression in male mice.•Postweaning stress induced synaptic remodeling in the mPFC in male mice.•Postweaning stress changed the gut microbial composition in male mice.