Gene expression profile of the hippocampus of rats subjected to chronic immobilization stress.

Gene expression profile of the hippocampus of rats subjected to chronic immobilization stress.
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慢性固定应激大鼠海马基因表达谱

DOI:
10.1371/journal.pone.0057621
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Bai MH
Bai MH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li XH;Chen JX;Yue GX;Liu YY;Zhao X;Guo XL;Liu Q;Jiang YM;Bai MH

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目的 本研究从全基因组水平系统探讨慢性应激对海马体的影响及其损伤机制。方法采用大鼠全基因组表达芯片(Illumina)检测慢性固定应激(每日固定应激3 h、7、21 d)大鼠海马区基因表达差异。通过基因本体论和生物信息学信号通路分析研究海马基因表达谱。还建立了差异表达的转录调控网络。采用实时定量聚合酶链反应(RT-PCR)验证微阵列结果并测定海马组织中Gabra1、Fadd、Crhr2和Cdk6基因的表达。结果 与对照组相比,应激7 d的大鼠海马共检测到602个差异表达基因,而应激21 d的大鼠海马共检测到566个差异表达基因。在7天和21天的压力下,压力显着抑制了动物海马体的初级免疫系统功能。暴露于应激 7 天后,固定激活了细胞外基质受体相互作用途径和细胞因子-细胞因子受体相互作用途径。 7天组海马组织胶原合成能力增强是应激调节网络的核心分子事件,而21天组海马细胞生长抑制是核心分子事件。对于 Gabra1、Fadd、Crhr2 和 Cdk6 基因,RT-PCR 结果与基因芯片检测结果几乎一致。结论 在7 d和21 d应激过程中,多基因、多层次、多信号通路的共同作用导致海马免疫功能紊乱、海马细胞凋亡和增殖失衡。
Objective This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. Methods The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinformatics. A differentially expressed transcription regulation network was also established. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine expression of the Gabra1, Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues. Results Compared to the control group, 602 differentially expressed genes were detected in the hippocampus of rats subjected to stress for 7 days, while 566 differentially expressed genes were expressed in the animals experiencing stress for 21 days. The stress significantly inhibited the primary immune system functions of the hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization activated the extracellular matrix receptor interaction pathway after 7 day exposure to stress and the cytokine-cytokine receptor interaction pathway. The enhanced collagen synthesis capacity of the hippocampal tissue was the core molecular event of the stress regulation network in the 7-day group, while the inhibition of hippocampal cell growth was the core molecular event in the 21-day group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in line with gene chip assay results. Conclusion During the 7-day and 21-day stress processes, the combined action of polygenic, multilevel, and multi-signal pathways leads to the disorder of the immunologic functions of the hippocampus, hippocampal apoptosis, and proliferation disequilibrium.
DOI: 10.1038/sj.onc.1202417
发表时间: 1999-02-11
期刊: ONCOGENE
影响因子: 8
作者:
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