Hippocampal gene expression changes underlying stress sensitization and recovery.
Hippocampal gene expression changes underlying stress sensitization and recovery.
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DOI：
10.1038/mp.2013.175
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发表时间：
2014-11
影响因子：
11
通讯作者：
McEwen BS
中科院分区：
文献类型：
--
作者：
Gray JD;Rubin TG;Hunter RG;McEwen BS
慢性和急性压力源与海马功能和焦虑样行为的变化有关。两者都会引起基因表达的变化，但这些变化在压力结束后持续的程度仍然知之甚少。作为表征应激后基因表达异常模式的重要第一步，本研究展示了慢性束缚应激 (CRS) 如何调节基因表达以响应野生型小鼠海马中的新应激源，以及这些变化在 CRS 结束后持续的程度。对雄性 C57/bl6 小鼠进行 1) 强迫游泳测试 (FST)，2) 皮质酮 (Cort) 或载体注射，3) CRS 21 天，然后进行 FST，或 4) 在 CRS 后恢复 21 天并进行 FST。提取海马 mRNA 并用于生成用于微阵列杂交的 cDNA 文库。初始急性应激源（FST 和媒介物注射）改变了相似的基因组，但 Cort 治疗产生了与 FST 和媒介物不同的特征。 CRS 后暴露于新的压力比未接触过的压力激活了更多且不同的基因。大多数因 CRS 增加的基因在恢复后有所减少，但许多基因仍然发生改变并且没有恢复到基线。通路分析发现了不同条件下显着的差异表达基因簇，最显着的是 NfKB 通路。定量 RT-PCR 验证了已知应激诱导基因中微阵列的变化，并确认了 NfKb 途径基因 Ikbα、RelA 和 Nfkb1 的变化。 FST 会增加 CRS 初始状态和恢复后的小鼠的焦虑样行为，但在 CRS 暴露后 24 小时的小鼠中则不会。这些发现表明，幼稚压力的影响与 Cort 升高不同，并且压力暴露史可以永久改变海马体中的基因表达模式以及对新压力源的行为反应。这些发现建立了正常恢复和压力适应的基线。重要的是，它们将作为概念基础，促进未来研究基因表达变化的细胞和区域基础，以及遗传风险因素和不良的早期生活经历，这些经历会导致情绪和焦虑症等压力恢复受损。
Chronic and acute stressors have been linked to changes in hippocampal function and anxiety-like behaviors. Both produce changes in gene expression, but the extent to which these changes endure beyond the end of stress remains poorly understood. As an essential first step to characterize abnormal patterns of gene expression after stress, this study demonstrates how chronic restraint stress (CRS) modulates gene expression in response to a novel stressor in the hippocampus of wild type mice and the extent to which these changes last beyond the end of CRS. Male C57/bl6 mice were subjected to 1) a forced swim test (FST), 2) Corticosterone (Cort) or vehicle injections, 3) CRS for 21 days and then a FST, or 4) allowed to recover 21 days after CRS and subjected to FST. Hippocampal mRNA was extracted and used to generate cDNA libraries for microarray hybridization. Naïve acute stressors (FST and vehicle injection) altered similar sets of genes, but Cort treatment produced a profile that was distinct from both FST and vehicle. Exposure to a novel stress after CRS activated substantially more and different genes than naïve exposure. Most genes increased by CRS were decreased after recovery, but many remained altered and did not return to baseline. Pathway analysis identified significant clusters of differentially expressed genes across conditions, most notably the NfKB pathway. Quantitative RT-PCR validated changes from the microarrays in known stress-induced genes and confirmed alterations in the NfKb pathway genes, Ikbα, RelA and Nfkb1. FST increased anxiety-like behavior in both the naïve and recovery from CRS conditions, but not in mice 24hrs subsequent to their CRS exposure. These findings suggest the effects of naïve stress are distinct from Cort elevation and that a history of stress exposure can permanently alter gene expression patterns in the hippocampus and the behavioral response to a novel stressor. These findings establish a baseline profile of normal recovery and adaptation to stress. Importantly, they will serve as a conceptual basis to facilitate the future study of the cellular and regional basis of gene expression changes as well as genetic risk factors and adverse early life experiences that lead to impaired recovery from stress such as occurs in mood and anxiety disorders.
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影响因子：
3.5
作者：
Datson, Nicole A.;Speksnijder, Niels;Lucassen, Paul J.
通讯作者：
Lucassen, Paul J.
影响因子：
2.5
作者：
BULLITT, E
通讯作者：
BULLITT, E
DOI：
10.1073/pnas.0911143106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Hunter, Richard G.;McCarthy, Katharine J.;McEwen, Bruce S.
通讯作者：
McEwen, Bruce S.
影响因子：
3.5
作者：
Marmigère, F;Givalois, L;Tapia-Arancibia, L
通讯作者：
Tapia-Arancibia, L
影响因子：
2.9
作者：
Ejchel-Cohen, Tatiana F.;Wood, Gwendolyn E.;Young, L. Trevor
通讯作者：
Young, L. Trevor