Interactions between chronic psychosocial stress and the endogenous clock

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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.