Dynamic proteomic analysis of protein expression profiles in whole brain of Balb/c mice subjected to unpredictable chronic mild stress: Implications for depressive disorders and future therapies
Dynamic proteomic analysis of protein expression profiles in whole brain of Balb/c mice subjected to unpredictable chronic mild stress: Implications for depressive disorders and future therapies
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DOI：
10.1016/j.neuint.2011.02.019
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发表时间：
2011-07-01
影响因子：
4.2
通讯作者：
Zuo, Pingping
中科院分区：
文献类型：
--
作者：
Liu, Yanyong;Yang, Nan;Zuo, Pingping
抑郁症的病因学和病理生理学仍不清楚。以往的研究大多是在单个观察时间点上进行的，这可能不足以揭示疾病发展过程中发生的分子事件。成年BALB/c小鼠暴露于不可预知的慢性轻度应激（UCMS）不同时间，采用差异化二维凝胶电泳（DICE）方法对脑组织进行分析，探讨其分子疾病特征。应激状态下皮质酮水平持续升高，提示应激状态下丘脑-垂体-肾上腺（HPA）轴功能亢进。行为学结果显示UCMS染毒小鼠出现抑郁改变。蛋白质组学分析表明，应激条件下能量动员异常伴随着活性氧（reactive oxygen species，ROS）的过度产生和内质网（endoplasmic reticulum，ER）应激。细胞骨架蛋白和抗氧化酶也发生了变化。生化和免疫组化结果证实了DICE分析所鉴定的变化。这些结果表明，ATP合成不足、ROS大量产生和内质网应激导致细胞骨架损伤和抗氧化蛋白表达抑制，最终导致功能性神经元凋亡或死亡。表达受影响的蛋白质可能为潜在的治疗策略提供工具。(C)2011爱思唯尔有限公司版权所有。
The etiology and pathophysiology of depression remain unknown. Previous works were mostly performed on single observation time-point which might be insufficiently to reveal the molecular events changed during the disease development. Adult BALB/c mice were exposed to unpredictable chronic mild stress (UCMS) for different periods and differential 2D gel electrophoresis (DICE) approach was employed to the brain tissue to explore the molecular disease signatures. Sustained elevation of corticosterone level was observed, suggesting the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis when the mice were subjected to the stressful situation. The behavioral results indicated the depressive alterations of the mice exposing to UCMS. The altered proteins identified by proteomics showed that abnormal energy mobilization under stress condition was accompanied by overproduction of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Cytoskeleton protein and antioxidant enzymes were also changed by UCMS treatment. The results of biochemical and immunohistochemical assay confirmed the changes identified by DICE analysis. These results indicated that the insufficiency of ATP synthesis, overwhelming ROS production and ER stress subsequently contributed to the cytoskeletal damage and inhibition to expression of some anti-oxidant proteins, which might ultimately bring functional neuron to apoptosis or death. Proteins whose expression is affected may provide tools for potential treatment strategies. (C) 2011 Elsevier Ltd. All rights reserved.