Neurobiology of chronic mild stress: parallels to major depression.
Neurobiology of chronic mild stress: parallels to major depression.
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DOI：
10.1016/j.neubiorev.2012.07.001
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发表时间：
2012-10
影响因子：
8.2
通讯作者：
Weinberg J
中科院分区：
文献类型：
--
作者：
Hill MN;Hellemans KG;Verma P;Gorzalka BB;Weinberg J
慢性轻度（或不可预测/可变）应激（CMS）模型是20多年前发展起来的抑郁症动物模型。该模型的基础是，在长期暴露于一系列温和但不可预测的压力源之后，动物会发展出一种奖励显著性受损的状态，类似于在重度抑郁症中观察到的快感缺乏。自建立以来，该模型也被用于各种研究，检查与抑郁症相关的神经生物学变量，尽管该模型从未被严格检查过，以验证CMS引起的神经生物学变化与抑郁症中记录的变化相似。本文综述了慢性轻度应激对神经生物学变量的影响，如神经化学、神经化学受体表达和功能、神经营养因子表达和细胞可塑性等方面的研究进展。然后将这些发现与临床研究的结果进行比较，这些研究检查了抑郁症人群的常见变量，以确定慢性轻度压力后观察到的变化是否与重度抑郁症中观察到的变化一致。我们得出的结论是，慢性轻度应激范式：(1)引起一系列与抑郁症相关的神经生物学变化；(2)可能是研究抑郁症中可能受到干扰的新系统的合适工具，从而有助于开发治疗抑郁症的新靶点。
The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression.