Faculty
Faculty Publications
Impact of Circadian Nuclear Receptor REV-ERBα on Midbrain Dopamine Production and Mood Regulation | |
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Year of publication | 2014 |
Title of paper | Impact of Circadian Nuclear Receptor REV-ERBα on Midbrain Dopamine Production and Mood Regulation |
Author | Sooyoung Chung, Eun Jeong Lee, Seongsik Yun, Han Kyoung Choe, Seong-Beom Park, Hyo Jin Son, Kwang-Soo Kim, Dean E. Dluzen, Inah Lee, Onyou Hwang, Gi Hoon Son, Kyungjin Kim |
Publication in journal | Cell |
Status of publication | accepted |
Vol | 157 |
Link | http://www.cell.com/cell/pdf/S0092-8674(14)00414-0.pdf 268회 연결 |
The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. Here, we show that the circadian nuclear receptor REVERBa, which is associated with bipolar disorder, impacts midbrain dopamine production and mood related behavior in mice. Genetic deletion of the Rev-erba gene or pharmacological inhibition of REV-ERBa activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. Also, REV-ERBa repressed tyrosine hydroxylase (TH) gene transcription via competition with nuclear receptor-related 1 protein (NURR1), another nuclear receptor crucial for dopaminergic neuronal function, thereby driving circadian TH expression through a target-dependent antagonistic mechanism. In conclusion, we identified a molecular connection between the circadian timing system and mood regulation, suggesting that REVERBa could be targeting in the treatment of circadian rhythm-related affective disorders. |