Qiao Yajun, Chen Hanxi, Guo Juan, Zhang Xingfang, Liang Xinxin, Wei Lixin, Wang Qiannan, Bi Hongtao, Gao Tingting
Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, China.
School of Psychology, Chengdu Medical College, Chengdu, China.
CNS Neurosci Ther. 2025 May;31(5):e70433. doi: 10.1111/cns.70433.
Stress is closely related to life, and it can also cause many mental disorders. However, there are significant sex differences in neuropsychiatric disorders associated with stress, particularly in depression, where the lifetime risk of depression in women is approximately twice that of men. However, the specific mechanism of this process has not been explained in detail.
Chronic restraint stress (CRS) + chronic and unpredictable mild stress (CUMS) was used to simulate social stress, and behavioral experiments, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, and metabolomics analysis of hippocampal and intestinal contents were performed.
The results showed that stress induced anxiety-like behavior in female mice and depression-like behavior in male mice. Sex differences in behavior may be related to monoamine neurotransmitters, hyperactivity of HPA axis, inflammatory factors, gut microbiota, and brain-gut metabolism. It is worth noting that stress caused opposite trends in DA (dopamine) levels, abundance of f-lactobaciliaceae, and levels of metabolites (1, 2-distearoyl-SN-glycero-3-phosphocholine) and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z)) in male and female mice.
The difference in neurotransmitter levels, the disorder of gut microbiota, and the abnormal brain and gut metabolism may lead to the gender difference in stress behavior.
压力与生活密切相关，还会引发多种精神障碍。然而，与压力相关的神经精神疾病存在显著的性别差异，尤其是在抑郁症方面，女性患抑郁症的终生风险约为男性的两倍。不过，这一过程的具体机制尚未得到详细解释。
采用慢性束缚应激（CRS）+慢性不可预测轻度应激（CUMS）来模拟社会压力，并进行行为实验、直肠和海马病理切片的苏木精-伊红（HE）染色、检测与抑郁相关的生物学指标、分析肠道菌群多样性以及对海马和肠道内容物进行代谢组学分析。
结果表明，压力在雌性小鼠中诱发了焦虑样行为，在雄性小鼠中诱发了抑郁样行为。行为上的性别差异可能与单胺类神经递质、下丘脑-垂体-肾上腺（HPA）轴功能亢进、炎症因子、肠道微生物群以及脑-肠代谢有关。值得注意的是，压力导致雄性和雌性小鼠体内多巴胺（DA）水平、f-乳酸杆菌科丰度以及代谢物（1,2-二硬脂酰-sn-甘油-3-磷酸胆碱）和PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z))水平呈现相反的变化趋势。
神经递质水平的差异、肠道微生物群的紊乱以及脑-肠代谢异常可能导致压力行为的性别差异。
