Differential phosphoproteome regulation of nucleus accumbens in environmentally enriched and isolated rats in response to acute stress.
Differential phosphoproteome regulation of nucleus accumbens in environmentally enriched and isolated rats in response to acute stress.
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DOI：
10.1371/journal.pone.0079893
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Green TA
中科院分区：
文献类型：
--
作者：
Fan X;Li D;Zhang Y;Green TA
越来越多的证据表明，应激与抑郁症的发病机制有关，抑郁症是一种严重的神经精神障碍，影响着世界上超过10%的人口。我们之前的研究表明，与在隔离环境中饲养的大鼠相比，在丰富环境中饲养的大鼠表现出较少的抑郁相关行为，这意味着环境丰富会产生抗抑郁药物样的行为表型。然而，其分子机制尚不完全清楚。蛋白质磷酸化迅速改变信号通路的功能，并改变与应激诱导的抑郁障碍相关的蛋白质的功能。因此，在这项研究中，我们使用磷酸蛋白质组学的方法来揭示在基础条件下隔离(IC)和丰富的环境条件(EC)以及对急性应激的响应下，大鼠伏隔核中不同的磷酸蛋白调节。我们发现在基础状态下EC与IC大鼠有23个磷蛋白被调节，IC大鼠有10个受应激调节的磷蛋白，EC大鼠有15个受应激调节。在所有显著调控的磷蛋白中，有11个至少在两种情况下存在。受调控的磷蛋白包括信号通路蛋白(包括ERK2)、酶、转录调节因子、蛋白质翻译调节因子、转运蛋白、伴侣蛋白和细胞骨架蛋白。这些发现为进一步了解蛋白质磷酸化在抑郁症发病机制和抗抑郁作用中的作用提供了一个全球性的视角。
Increasing evidence shows that stress contributes to the pathogenesis of major depressive disorder which is a severe neuropsychiatric disorder and influences over 10% of the world's population. Our previous studies revealed that rats reared in an enriched environment display less depression-related behavior compared to rats raised in an isolated environment, which implies that environmental enrichment produces an antidepressant-like behavioral phenotype. However, the molecular mechanisms are not fully understood. Protein phosphorylation rapidly changes signaling pathway function and alters the function of proteins associated with the stress-induced depressive disorder. Thus, in this study, a phosphoproteomic approach was used to uncover differential phosphoprotein regulation in rat nucleus accumbens between isolated (IC) and enriched environmental conditions (EC) under basal conditions, and in response to acute stress. We found 23 phosphoproteins were regulated in EC vs. IC rats under basal conditions; 10 phosphoproteins regulated by stress in IC rats; and 15 regulated by stress in EC rats. Among all significantly regulated phosphoproteins, 11 of them were represented in at least two conditions. The regulated phosphoproteins represent signaling pathway proteins (including ERK2), enzymes, transcriptional regulators, protein translation regulators, transporters, chaperones and cytoskeletal proteins. These findings provide a global view for further understanding the contribution of protein phosphorylation in depression pathogenesis and antidepressant action.
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