{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7(1)"],"submitter":["Park I"],"pubmed_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."],"journal":["Communications biology"],"pagination":["998"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11327353"],"repository":["biostudies-literature"],"pubmed_title":["Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation."],"pmcid":["PMC11327353"],"pubmed_authors":["Kim D","Park I","Kim K","Kim J","Choi JW","Choe HK","Choi M","Moon C","Jang S","Yu SW","Geum D","Choe Y","Son GH"],"additional_accession":[]},"is_claimable":false,"name":"Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2025-04-19T20:39:52.803Z","creation":"2025-04-19T20:39:52.803Z"},"accession":"S-EPMC11327353","cross_references":{"pubmed":["39147805"],"doi":["10.1038/s42003-024-06647-y"]}}