Repeated psychosocial stress at night, but not day, affects the central molecular clock
Repeated psychosocial stress at night, but not day, affects the central molecular clock
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DOI：
10.3109/07420528.2014.940085
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发表时间：
2014-11-01
影响因子：
2.8
通讯作者：
Lundkvist, Gabriella B. S.
中科院分区：
文献类型：
--
作者：
Bartlang, Manuela S.;Savelyev, Sergey A.;Lundkvist, Gabriella B. S.
我们最近已经证明，在雄性C57BL/6小鼠的黑暗/活动阶段施加重复社会失败(SD)对行为、生理和免疫学的影响比在光明/非活动阶段更负面。在这里，我们研究了相同的应激范式，它结合了心理社会和新奇应激源，通过让转基因Perod2：：荧光素酶(PER2：：Luc)和野生型(WT)小鼠在19天的早期光明阶段(社会失败光=SDL)或早期黑暗阶段(社会失败暗=SDD)接受重复的SD，对生物钟的影响进行了研究。分析视交叉上核(SCN)和肾上腺的PER2：：Luc节律和Clock基因的表达，并检测SCN中PER2蛋白的表达。与独居对照组(SHC)和SDL小鼠相比，SDD小鼠SCN的PER2：：Luc节律幅度增加，肾上腺的PER2和Cryptochrome1mRNA表达降低，SCN后部的PER2蛋白表达增加。而SDL小鼠SCN的PER2：：Luc节律未受影响。然而，与SHC小鼠相比，SDL小鼠的肾上腺PER2：：Luc节律提前了2小时。此外，SDL小鼠的血浆脑源性神经营养因子(BDNF)水平和SCN中的BDNF mRNA水平升高。综上所述，这些结果表明，SCN的分子节律性受重复SDD的影响，而SDL不影响，而肾上腺外周时钟主要受SDL的影响。在SDL组中观察到的脑源性神经营养因子的增加可能起到了保护作用，以抵御反复的心理社会应激的负面后果。
We have recently demonstrated that the outcome of repeated social defeat (SD) on behavior, physiology and immunology is more negative when applied during the dark/active phase as compared with the light/inactive phase of male C57BL/6 mice. Here, we investigated the effects of the same stress paradigm, which combines a psychosocial and novelty stressor, on the circadian clock in transgenic PERIOD2::LUCIFERASE (PER2::LUC) and wildtype (WT) mice by subjecting them to repeated SD, either in the early light phase (social defeat light = SDL) or in the early dark phase (social defeat dark = SDD) across 19 days. The PER2::LUC rhythms and clock gene mRNA expression were analyzed in the suprachiasmatic nucleus (SCN) and the adrenal gland, and PER2 protein expression in the SCN was assessed. SDD mice showed increased PER2::LUC rhythm amplitude in the SCN, reduced Per2 and Cryptochrome1 mRNA expression in the adrenal gland, and increased PER2 protein expression in the posterior part of the SCN compared with single-housed control (SHC) and SDL mice. In contrast, PER2::LUC rhythms in the SCN of SDL mice were not affected. However, SDL mice exhibited a 2-hour phase advance of the PER2::LUC rhythm in the adrenal gland compared to SHC mice. Furthermore, plasma levels of brain-derived neurotrophic factor (BDNF) and BDNF mRNA in the SCN were elevated in SDL mice. Taken together, these results show that the SCN molecular rhythmicity is affected by repeated SDD, but not SDL, while the adrenal peripheral clock is influenced mainly by SDL. The observed increase in BDNF in the SDL group may act to protect against the negative consequences of repeated psychosocial stress.