Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains.
Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains.
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DOI：
10.1186/s12864-015-1431-6
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发表时间：
2015-04-03
期刊：
影响因子：
4.4
通讯作者：
Schalkwyk LC
中科院分区：
文献类型：
--
作者：
Malki K;Mineur YS;Tosto MG;Campbell J;Karia P;Jumabhoy I;Sluyter F;Crusio WE;Schalkwyk LC
BALB/cJ 是一种对压力敏感的品系，并且极易受到对慢性压力源的反应而产生缺陷的享乐影响。该菌株作为研究压力相关疾病的动物模型提供了很大的前景。我们提出了一项关于不可预测的慢性轻度应激对 BALB/cJ 和 C57BL/6J 小鼠的影响的海马基因表达比较研究。使用 Affymetrix MOE 430 测量 16 只不同品系（BALB/cJ 和 C57BL/6J）的两性动物的海马基因表达，这些动物受到不可预测的慢性轻度应激 (UCMS) 或无应激。通过监督和无监督线性模型并使用加权基因共表达网络分析（WGCNA）对差异进行统计评估。为了进一步了解与压力反应相关的机制，我们在荟萃分析设计中使用 WGCNA 与 GENDEP 项目的并行研究交叉验证了我们的结果。 UCMS 的效果通过主成分分析可见，它突出了 BALB/cJ 应变的应力敏感性。发现了许多与应激反应相关的基因和基因网络，包括 Creb1 基因。 WGCNA 和通路分析揭示了以 Nfkb1 为中心的基因网络。荟萃分析的结果揭示了一条以泛素 C (Ubc) 基因为中心的非常重要的基因通路。所有被发现的途径都与炎症和免疫反应有关。该研究使用 GxE 设计研究了动物模型对不利环境反应的分子机制。通过 PCA 分析，在基因组水平上可以看到与压力相关的差异，突显 BALB/cJ 动物对环境压力源的高度敏感性。报道的几个候选基因和基因网络与炎症和神经发生有关，可以为人类研究中的候选基因选择提供信息，并为重度抑郁症的病理学提供更多见解。本文的在线版本 (doi:10.1186/s12864-015-1431-6) 包含补充材料，可供授权用户使用。
BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and C57BL/6J) of both sexes and subjected to either unpredictable chronic mild stress (UCMS) or no stress. Differences were statistically evaluated through supervised and unsupervised linear modelling and using Weighted Gene Coexpression Network Analysis (WGCNA). In order to gain further understanding into mechanisms related to stress response, we cross-validated our results with a parallel study from the GENDEP project using WGCNA in a meta-analysis design. The effects of UCMS are visible through Principal Component Analysis which highlights the stress sensitivity of the BALB/cJ strain. A number of genes and gene networks related to stress response were uncovered including the Creb1 gene. WGCNA and pathway analysis revealed a gene network centered on Nfkb1. Results from the meta-analysis revealed a highly significant gene pathway centred on the Ubiquitin C (Ubc) gene. All pathways uncovered are associated with inflammation and immune response. The study investigated the molecular mechanisms underlying the response to adverse environment in an animal model using a GxE design. Stress-related differences were visible at the genomic level through PCA analysis highlighting the high sensitivity of BALB/cJ animals to environmental stressors. Several candidate genes and gene networks reported are associated with inflammation and neurogenesis and could serve to inform candidate gene selection in human studies and provide additional insight into the pathology of Major Depressive Disorder. The online version of this article (doi:10.1186/s12864-015-1431-6) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
2.6
作者：
Binder, Elke;Malki, Karim;Schalkwyk, Leonard C.
通讯作者：
Schalkwyk, Leonard C.
影响因子：
3.4
作者：
Fernandes, C;Paya-Cano, JL;Schalkwyk, LC
通讯作者：
Schalkwyk, LC
影响因子：
--
作者：
Kessler, RC;Berglund, P;Walters, EE
通讯作者：
Walters, EE
影响因子：
2.4
作者：
Kaufmann, Ines;Eisner, Christoph;Thiel, Manfred
通讯作者：
Thiel, Manfred