{Reference Type}: Journal Article
{Title}: Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.
{Author}: Park I;Choi M;Kim J;Jang S;Kim D;Kim J;Choe Y;Geum D;Yu SW;Choi JW;Moon C;Choe HK;Son GH;Kim K;
{Journal}: Commun Biol
{Volume}: 7
{Issue}: 1
{Year}: 2024 Aug 15
{Factor}: 6.548
{DOI}: 10.1038/s42003-024-06647-y
{Abstract}: Affective disorders are frequently associated with disrupted circadian rhythms. The existence of rhythmic secretion of central serotonin (5-hydroxytryptamine, 5-HT) pattern has been reported; however, the functional mechanism underlying the circadian control of 5-HTergic mood regulation remains largely unknown. Here, we investigate the role of the circadian nuclear receptor REV-ERBα in regulating tryptophan hydroxylase 2 (Tph2), the rate-limiting enzyme of 5-HT synthesis. We demonstrate that the REV-ERBα expressed in dorsal raphe (DR) 5-HTergic neurons functionally competes with PET-1-a nuclear activator crucial for 5-HTergic neuron development. In mice, genetic ablation of DR 5-HTergic REV-ERBα increases Tph2 expression, leading to elevated DR 5-HT levels and reduced depression-like behaviors at dusk. Further, pharmacological manipulation of the mice DR REV-ERBα activity increases DR 5-HT levels and affects despair-related behaviors. Our findings provide valuable insights into the molecular and cellular link between the circadian rhythm and the mood-controlling DR 5-HTergic systems.