Department of Medical Care, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated 6th People's Hospital, Shanghai 200233, China.
Horm Behav. 2020 Jun;122:104741. doi: 10.1016/j.yhbeh.2020.104741. Epub 2020 Mar 16.
Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.
社交接触是否有助于抑郁的潜在机制以及观察到的性别差异尚不清楚。在这项研究中，我们让年轻雄性和雌性小鼠接受分离和束缚应激 4 周，并评估行为、神经递质水平、激素和炎症细胞因子。结果表明，与对照组相比，应激暴露的雄性小鼠在第 1 周后体重和蔗糖偏好明显下降。在第 4 周，它们表现出更高程度的焦虑（旷场试验）和抑郁样行为（强迫游泳试验）。此外，雄性小鼠纹状体中单胺神经递质，包括去甲肾上腺素和多巴胺显著减少，血清中促炎细胞因子，如肿瘤坏死因子 α 和白细胞介素 1β 增加。相比之下，雌性小鼠在应激期间持续减重，应激后蔗糖偏好明显下降。重要的是，只有雌性而不是雄性小鼠表现出下丘脑-垂体-肾上腺（HPA）轴的激活，促肾上腺皮质激素水平显著升高。此外，c-fos 和 AVP 的 mRNA 水平显示应激和性别之间存在显著的相互作用。最后，我们得出结论，HPA 轴和炎症的失衡可能是分离/束缚诱导的抑郁行为性别差异的重要原因，而这种变化可能是由 c-fos 和 AVP 介导的。
