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- Title
Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.
- Authors
Park, Inah; Choi, Mijung; Kim, Jeongah; Jang, Sangwon; Kim, Doyeon; Kim, Jihoon; Choe, Youngshik; Geum, Dongho; Yu, Seong-Woon; Choi, Ji-Woong; Moon, Cheil; Choe, Han Kyoung; Son, Gi Hoon; Kim, Kyungjin
- 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. Circadian nuclear receptor, REV-ERBa regulates the rhythmic serotonin synthesis in the central nervous system, highlighting the molecular connections between circadian clock and mood regulation
- Subjects
SEROTONIN receptors; MOOD (Psychology); RAPHE nuclei; SEROTONIN; TRYPTOPHAN hydroxylase; AFFECTIVE disorders; NEURON development
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-024-06647-y