Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor rev-erbα
Research output: Contribution to journal › Journal article › Research › peer-review
The regulation of behavior by the molecular components of the circadian clock is not well understood. Here we report that mice lacking the nuclear receptor Rev-erbα, a potent transcriptional repressor and core clock component, displayed marked hyperactivity and impaired response habituation in novel environments. In addition, Rev-erbα knockout (KO) mice were deficient in short-term, long-term, and contextual memories and also showed impairment in nest-building ability. Together, these results suggest that Rev-erbα KO mice manifest defective hippocampal function. Interestingly, the changes in novelty-induced locomotor activity of Rev-erbα KO mice were comparable at multiple times of day, potentially due to the muted amplitude of Rev-erbα oscillation in the hippocampus of wild-type mice. Hippocampal dopamine turnover was increased in Rev-erbα KO mice, due to up-regulation of tyrosine hydroxylase, the rate-limiting enzyme in dopamine production, and pharmacologic inhibition of tyrosine hydroxylase activity partially rescued locomotor hyperactivity. These findings reveal a novel, nonredundant function for Rev-erbα that links a core component of the circadian gene-regulatory network to the control of dopaminergic and hippocampus-dependent behaviors.
Original language | English |
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Journal | Molecular Endocrinology |
Volume | 28 |
Issue number | 4 |
Pages (from-to) | 490-498 |
Number of pages | 9 |
ISSN | 0888-8809 |
DOIs | |
Publication status | Published - 2014 |
ID: 347794269