Interactions between chronic psychosocial stress and the endogenous clock

慢性心理社会压力和生物钟的失调有许多共同的特征。两者都对健康和寿命有重大影响，都显著影响HPA轴，影响糖皮质激素(GC)水平和免疫反应，并且都使用相似的神经肽作为信号分子。从解剖学上讲，视交叉上核(SCN)中的HPA轴和生物钟共享一个共同的界面--室旁核(PVN)。在PVN内，合成促肾上腺皮质激素释放因子(CRF)的神经元是应激反应并触发肾上腺GC分泌。PVN也接受来自SCN的输入，SCN独立于应激调节GC分泌的昼夜节律。每天的GC峰值为动物的活动期做好了准备。这个项目将研究心理社会压力和SCN生物钟之间的相互作用。我们将确定(I)生物钟是否以一种白天依赖的方式调节应对压力的能力，以及(Ii)心理社会压力是否依赖于应激源暴露的时间来影响生物钟。为此，我们将让小鼠在早晨或晚上接受反复的社会失败(SD)应激，并研究湿润的生理应激反应对SCN节律行为和分子昼夜振荡的影响。

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.