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Interactions between chronic psychosocial stress and the endogenous clock

慢性社会心理压力与内源时钟之间的相互作用

基本信息

批准号：
196358657
负责人：
Professorin Dr. Charlotte Förster
金额：
--
依托单位：
Lehrstuhl für Neurobiologie und Genetik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/196358657?language=en
关键词：
Interactions between chronic psychosocial stress

项目摘要

Chronic psychosocial stress and dys-reg ulation of the circadian clock share many common features. Both have dramatic consequences on health and life span, both prominently affect the HPA axis influencing glucocorticoid (GC) levels and immune responses, and both employ similar neuropeptides as signalling molecules. Anatomically, the HPA axis and the circadian clock in the suprachiasmatic nuclei (SCN) share a common interface - the paraventricular nucleus (PVN). Within the PVN, corticotrophin releasing factor (CRF) synthesizing neurons are stress responsive and trigger adrenal GC secretion. The PVN also receives inputs from the SCN, which regulates the circadian rhythm of GC secretion independent of stress. The daily GC peak prepares the animal for its active phase. This project will investigate the mutual interactions between psychosocial stress and the circadian clock in the SCN. We will determine (i) whether the circadian clock modulates the capability to cope with stress in a daytime dependent manner and (ii) whether psychosocial stress affects the circadian clock in dependence on the time of stressor exposure. To do so, we will subject mice to repeated social defeat (SD) stress in the morning or evening and investigate the physiological stress responses as wett as the consequences on rhythmic behaviour and molecular circadian oscillations in the SCN.

慢性心理社会压力和生物钟失调有许多共同的特征。两者都对健康和寿命有显著影响，都显著影响糖皮质激素（GC）水平和免疫反应的HPA轴，并且都采用类似的神经肽作为信号分子。在解剖学上，HPA轴和视交叉上核（SCN）中的昼夜节律钟共享一个共同的界面-室旁核（PVN）。在PVN内，促肾上腺皮质激素释放因子（CRF）合成神经元是应激反应性的，并触发肾上腺GC分泌。PVN还接收来自SCN的输入，SCN独立于应激调节GC分泌的昼夜节律。每日GC峰使动物为其活动期做好准备。本研究将探讨心理社会压力与SCN生物钟之间的相互作用。我们将确定（i）生物钟是否以白天依赖的方式调节科普压力的能力，以及（ii）心理社会压力是否会影响生物钟依赖于压力源暴露的时间。为此，我们将使小鼠在早晨或晚上经受重复的社交失败（SD）应激，并研究生理应激反应以及对SCN中的节律行为和分子昼夜节律振荡的后果。