Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression
Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression
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下丘脑-垂体-肾上腺轴失衡和炎症导致分离和束缚引起的抑郁症的性别差异
DOI：
10.1016/j.yhbeh.2020.104741
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发表时间：
2020-06-01
影响因子：
3.5
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Dong, Yinfeng;Wang, Xuyang;Hu, Gang
社会接触是否有助于抑郁症的潜在机制和观察到的性别差异尚不清楚。在这项研究中，我们对年轻的雄性和雌性小鼠进行了为期4周的分离和限制诱导的压力，并评估了行为，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，暴露于应激1周后，雄性小鼠的体重和蔗糖偏好显着下降。在第四周，他们表现出更高程度的焦虑（开放领域测试）和抑郁样行为（强迫游泳测试）。此外，雄性动物的单胺神经递质（包括纹状体中的去甲肾上腺素和多巴胺）显著减少，促炎细胞因子（如血清中的肿瘤坏死因子α和白细胞介素1 β）增加。与此相反，女性表现出持续的体重下降，在压力和压力后，蔗糖的偏好显着下降。重要的是，雌性而非雄性显示下丘脑-垂体-肾上腺（HPA）轴激活，促肾上腺皮质激素水平显著升高。此外，c-fos和AVP的mRNA水平表明应激与性别之间存在显着的相互作用。最后，我们得出结论，HPA轴和炎症的不平衡可能是重要的贡献者的性别差异分离/限制引起的抑郁行为，这种变化可能是由c-fos和AVP介导的。
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 alpha and interleukin 1 beta 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.