Long-term (intergenerational) effects of chronic stress on mouse behavior and its interaction with the circadian gene regulation in the hippocampus

Almost daily we face stressful situations and the body reacts with various coping mechanisms. Consequently, glucocorticoids are released, leading to immunosuppression and a changed metabolism. However, if the stress becomes chronic, the coping systems can be maladaptively altered. In addition, glucocorticoid levels follow a daily circadian rhythm with a peak in the morning just before the organism starts to become active. While it is known that chronic stress can lead to a disruption of the circadian rhythm, it is still not fully understood how the long-term effects after chronic stress and the circadian rhythm interact on a molecular level. We address this question by assessing the transcriptome of the rodent hippocampus, a brain region critically involved in stress response behavior at the circadian high or low once a chronic stressor has subsided. We observe a persistent behavioral alterations as assed by automated tracking and sophisticated machine learning analysis, suggesting functional relevance of the disruption of circadian control of gene expression.