Laboratory for Behavioral Neurophysiology of Memory

Publications

Publications

Impact of circadian nuclear receptor REV-ERBalpha on midbrain dopaime production and mood regulation.
Year of publication 2014
Title of paper Impact of circadian nuclear receptor REV-ERBalpha on midbrain dopaime production and mood regulation.
Author Chung, S., Lee, E.J., Yun, S., Choe, H.K., Park, S.B., Son, H.J., Kim, K.S., Diuzen, D.E., Lee, I., Hwang, O., Son, G.H., and Kim, K.J.
Publication in journal Cell
Status of publication published
Vol 157
File 첨부 chung_cell_2014.pdf (2.1M) 14회 다운로드 DATE : 2017-06-06 16:53:42

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.