Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid
Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid
复制标题
慢性轻度应激对行为和神经生物学参数的影响 – 糖皮质激素的作用
DOI：
10.1016/j.yhbeh.2015.11.006
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发表时间：
2016-02-01
影响因子：
3.5
通讯作者：
Chen, Nai-hong
中科院分区：
文献类型：
--
作者：
Chen, Jiao;Wang, Zhen-zhen;Chen, Nai-hong
重度抑郁症被认为源于对不良事件的适应不良，特别是当与情绪相关的大脑区域发生损伤时。下丘脑-垂体-肾上腺（HPA）轴是参与生理应激反应的主要系统之一。 HPA 轴功能障碍和高糖皮质激素浓度在抑郁症的发病机制中起着重要作用。此外，星形胶质细胞的残疾和神经营养蛋白脑源性神经营养因子（BDNF）的功能障碍极大地影响抑郁症和焦虑症的发展。因此，我们研究了慢性轻度应激（CMS）暴露后肾上腺切除（ADX）大鼠在糖皮质激素生成和循环缺失的情况下是否表现出抑郁样和焦虑样行为及其潜在的分子机制。结果表明，糖皮质激素控制的大鼠在 CMS 后表现出焦虑样行为，但没有表现出抑郁样行为。分子和细胞变化包括海马 BDNF 减少、星形胶质细胞功能障碍（连接蛋白 43 (cx43) 减少）以及前额皮质 (PFC) 间隙连接异常。有趣的是，我们没有发现接受 CMS 的 ADX 大鼠海马或 PFC 中糖皮质激素受体 (GR) 或其伴侣蛋白 FK506 结合蛋白 51 (FKBP5) 表达有任何变化。总之，糖皮质激素的产生和循环是 CMS 引起的抑郁样行为的影响因素之一。相比之下，CMS 对焦虑样行为的影响与循环糖皮质激素的存在无关。同时，应激通过较高的糖皮质激素暴露降低了 GR 表达并增强了 FKBP5 表达。间隙连接功能障碍和 BDNF 变化可能与焦虑样行为有关。 (C) 2015 Elsevier Inc. 保留所有权利。
Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors. (C) 2015 Elsevier Inc. All rights reserved.