Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor rev-erbα
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor rev-erbα. / Jager, Jennifer; Timothy O'Brien, W.; Manlove, Jessica; Krizman, Elizabeth N.; Fang, Bin; Gerhart-Hines, Zachary; Robinson, Michael B.; Klein, Peter S.; Lazar, Mitchell A.
In: Molecular Endocrinology, Vol. 28, No. 4, 2014, p. 490-498.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor rev-erbα
AU - Jager, Jennifer
AU - Timothy O'Brien, W.
AU - Manlove, Jessica
AU - Krizman, Elizabeth N.
AU - Fang, Bin
AU - Gerhart-Hines, Zachary
AU - Robinson, Michael B.
AU - Klein, Peter S.
AU - Lazar, Mitchell A.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84897941566&partnerID=8YFLogxK
U2 - 10.1210/me.2013-1351
DO - 10.1210/me.2013-1351
M3 - Journal article
C2 - 24552589
AN - SCOPUS:84897941566
VL - 28
SP - 490
EP - 498
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 4
ER -
ID: 347794269