Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha 410013, China; Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Behav Brain Res. 2025 Jan 5;476:115262. doi: 10.1016/j.bbr.2024.115262. Epub 2024 Sep 19.
The gut microbiota plays a key role in the brain function impairment caused by chronic stress, yet its exact mechanism remains unclear. Many studies have revealed the important role of miR-124 in the central nervous system. Meanwhile, previous studies have indicated that miR-124 may be regulated by chronic stress and gut microbiota. Here, we aimed to explore whether miR-124 serves as a mediator for the impacts of gut microbial dysbiosis on brain function in mice subjected to chronic stress. Repeated daily restraint stress for 4 weeks was used to induce chronic stress in mice. Chronic stress resulted in gut microbial dysbiosis, abnormal behaviors, and a decrease in hippocampal miR-124 levels. Treatment with different probiotic mixtures significantly alleviated the effects of chronic stress on hippocampal miR-124 levels and mouse behaviors. Suppression of hippocampal miR-124 expression reversed the beneficial effects of probiotics on cognitive function, neurogenesis, and related molecular markers in chronically stressed mice. Bioinformatics analysis and qPCR suggested that Ptpn11 might be a target gene for miR-124 in mediating the effects of gut microbial dysbiosis on brain function in these mice. These findings suggest that miR-124 is a pivotal regulator that mediates the detrimental effects of gut microbial dysbiosis on brain function and the subsequent cognitive impairment during chronic stress.
肠道微生物群在慢性应激引起的大脑功能损伤中起着关键作用，但确切的机制尚不清楚。许多研究揭示了 miR-124 在中枢神经系统中的重要作用。同时，先前的研究表明，miR-124 可能受到慢性应激和肠道微生物群的调节。在这里，我们旨在探讨 miR-124 是否作为肠道微生物失调对慢性应激小鼠大脑功能影响的中介物。采用重复每日束缚应激 4 周的方法诱导小鼠慢性应激。慢性应激导致肠道微生物失调、异常行为和海马 miR-124 水平降低。用不同的益生菌混合物处理可显著减轻慢性应激对海马 miR-124 水平和小鼠行为的影响。抑制海马 miR-124 表达可逆转益生菌对慢性应激小鼠认知功能、神经发生和相关分子标志物的有益作用。生物信息学分析和 qPCR 表明，Ptpn11 可能是 miR-124 介导肠道微生物失调对这些小鼠大脑功能及随后认知损伤影响的靶基因。这些发现表明，miR-124 是一种关键的调节因子，介导了肠道微生物失调对大脑功能的有害影响，以及慢性应激期间随后的认知障碍。
