Chronic unpredictable stress (CUS)-induced anxiety and related mood disorders in a zebrafish model: altered brain proteome profile implicates mitochondrial dysfunction.
Chronic unpredictable stress (CUS)-induced anxiety and related mood disorders in a zebrafish model: altered brain proteome profile implicates mitochondrial dysfunction.
复制标题
DOI：
10.1371/journal.pone.0063302
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Idris MM
中科院分区：
文献类型：
--
作者：
Chakravarty S;Reddy BR;Sudhakar SR;Saxena S;Das T;Meghah V;Brahmendra Swamy CV;Kumar A;Idris MM
焦虑和抑郁是主要的慢性情绪障碍，每种疾病的病因似乎都是反复暴露于各种不可预测的压力因素。大多数关于焦虑和相关情绪障碍的研究都是在啮齿类动物中进行的，一个好的模型是慢性不可预测压力（CUS）。在这项研究中，我们试图了解最简单的脊椎动物模型斑马鱼中 CUS 诱发的情绪障碍的神经胶质细胞和行为变化的分子基础。斑马鱼接受 CUS 范式，其中每天使用两种不同的压力源，持续 15 天，并使用新型坦克测试、浅滩凝聚力和趋向性进行彻底的行为分析，以评估焦虑和相关情绪障碍表型。暴露于慢性压力源十五天似乎会诱发焦虑和相关的情绪障碍表型。在该斑马鱼模型中还观察到神经发生减少，这是啮齿类动物焦虑和相关疾病的另一个标志。啮齿动物焦虑和相关疾病的常见分子标记，促肾上腺皮质激素释放因子（CRF）、钙调神经磷酸酶（ppp3r1a）和磷酸环AMP反应元件结合蛋白（pCREB）也在鱼类模型中得到了复制。最后，使用 2DE FTMS/ITMSMS 蛋白质组学分析，发现 18 种蛋白质在斑马鱼焦虑和相关疾病中失调。受影响最大的过程是线粒体功能，根据啮齿动物和临床样本的报告，18 种差异调节蛋白中有 4 种是线粒体蛋白：PHB2、SLC25A5、VDAC3 和 IDH2。因此，斑马鱼 CUS 模型和蛋白质组学不仅可以促进焦虑和相关情绪障碍的新分子靶标的发现，还可以促进药物开发化合物的常规筛选。
Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development.
登录
查看更多内容
影响因子：
2.7
作者：
Egan, Rupert J.;Bergner, Carisa L.;Hart, Peter C.;Cachat, Jonathan M.;Canavello, Peter R.;Elegante, Marco F.;Elkhayat, Salem I.;Bartels, Brett K.;Tien, Anna K.;Tien, David H.;Mohnot, Sopan;Beeson, Esther;Glasgow, Eric;Amri, Hakima;Zukowska, Zofia;Kalueff, Allan V.
通讯作者：
Kalueff, Allan V.
影响因子：
4
作者：
Doyon, C;Trudeau, VL;Moon, TW
通讯作者：
Moon, TW
影响因子：
4.8
作者：
Hashimoto, M;Bar-on, P;Masliah, E
通讯作者：
Masliah, E
影响因子：
6.1
作者：
Hsieh J;Eisch AJ
通讯作者：
Eisch AJ
影响因子：
3.3
作者：
Brecht, S;Schwarze, K;Herdegen, T
通讯作者：
Herdegen, T