Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation

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

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

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 REV-ERBα, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erbα gene or pharmacological inhibition of REV-ERBα activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. Also, REV-ERBα 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 REV-ERBα could be targeting in the treatment of circadian rhythm-related affective disorders.

Original languageEnglish
Pages (from-to)858-868
Number of pages11
JournalCell
Volume157
Issue number4
DOIs
Publication statusPublished - 2014 May 8

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation'. Together they form a unique fingerprint.

  • Cite this

    Chung, S., Lee, E. J., Yun, S., Choe, H. K., Park, S. B., Son, H. J., Kim, K. S., Dluzen, D. E., Lee, I., Hwang, O., Son, G. H., & Kim, K. (2014). Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation. Cell, 157(4), 858-868. https://doi.org/10.1016/j.cell.2014.03.039