A novel supplemental circadian feedback loop in CA1 mediates mood-related behaviors

Traditional circadian clock feedback loops include positive branches and negative branches. Per genes belong to the negative branches. There are three subtypes of Per genes named Per1, Per2 and Per3. The relationship among these subtypes has been rarely reported. In this study, we aimed to explore the action between Per1 and Per2 genes, which are known to be critical in the pathogenesis of mood disorder. We revealed that Per1 has a positive action on the expression of Per2, while Per2 shows a negative effect on Per1 expression. This forms a novel feedback loop. Besides, both knockdown and over-expression of Per1 exhibit a pro-depressive effect, indicating a potential mediation in the pathogenesis of major depressive disorder. Correspondingly, knockdown of Per2 induces mania-like behavior, while, over-expression of Per2 produces a pro-depressive effect, suggesting its involvement in the pathophysiology of bipolar disorder. This research may provide an advance in the differential diagnosis between the two diseases in the future. HighlightsO_LIPer1 promotes the expression of Per2, while Per2 inhibit the expression of Per1 in CA1, forming a negative feedback loop. C_LIO_LIBoth knockdown and over-expression of Per1 in CA1 induce depression-like behaviors, while Per2 involves in both mania and depression-like behaviors. C_LI