School of Pre-clinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
PLoS One. 2013;8(3):e57621. doi: 10.1371/journal.pone.0057621. Epub 2013 Mar 27.
This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level.
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.
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.
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.
本研究系统地研究了慢性应激对海马体的影响及其在全基因组水平上的损伤机制。
采用大鼠全基因组表达芯片（Illumina）检测慢性束缚应激（每日束缚应激 3 小时，持续 7 天或 21 天）后大鼠海马体的基因表达差异。通过生物信息学对海马体基因表达谱进行基因本体和信号通路分析。还建立了一个差异表达的转录调控网络。实时定量聚合酶链反应（RT-PCR）用于验证微阵列结果，并确定海马组织中 Gabra1、Fadd、Crhr2 和 Cdk6 基因的表达。
与对照组相比，应激 7 天的大鼠海马体中检测到 602 个差异表达基因，而应激 21 天的大鼠海马体中表达了 566 个差异表达基因。应激显著抑制了应激 7 天和 21 天动物海马体的初级免疫系统功能。在应激 7 天暴露后，束缚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。海马组织胶原合成能力增强是应激调节网络在 7 天组中的核心分子事件，而海马细胞生长抑制是 21 天组中的核心分子事件。对于 Gabra1、Fadd、Crhr2 和 Cdk6 基因，RT-PCR 结果与基因芯片检测结果基本一致。
在 7 天和 21 天的应激过程中，多基因、多层次和多信号通路的共同作用导致海马体免疫功能紊乱、海马体凋亡和增殖失衡。
