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

Abstract

AbstractTraditional circadian clock feedback loops include positive branches and negative branches.Pergenes belong to the negative branches. There are three subtypes ofPergenes namedPer1, Per2andPer3. The relationship among these subtypes has been rarely reported. In this study, we aimed to explore the action betweenPer1andPer2genes, which are known to be critical in the pathogenesis of mood disorder. We revealed thatPer1has a positive action on the expression ofPer2, whilePer2shows a negative effect onPer1expression. This forms a novel feedback loop. Besides, both knockdown and over-expression ofPer1exhibit a pro-depressive effect, indicating a potential mediation in the pathogenesis of major depressive disorder. Correspondingly, knockdown ofPer2induces mania-like behavior, while, over-expression ofPer2produces 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.HighlightsPer1promotes the expression ofPer2, whilePer2inhibit the expression ofPer1in CA1, forming a negative feedback loop.Both knockdown and over-expression ofPer1in CA1 induce depression-like behaviors, whilePer2involves in both mania and depression-like behaviors.