RT Journal Article
SR Electronic
T1 Circadian Modulation of Dopamine Levels and Dopaminergic Neuron Development Contributes to Attention Deficiency and Hyperactive Behavior
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2572
OP 2587
DO 10.1523/JNEUROSCI.2551-14.2015
VO 35
IS 6
A1 Jian Huang
A1 Zhaomin Zhong
A1 Mingyong Wang
A1 Xifeng Chen
A1 Yicheng Tan
A1 Shuqing Zhang
A1 Wei He
A1 Xiong He
A1 Guodong Huang
A1 Haiping Lu
A1 Ping Wu
A1 Yi Che
A1 Yi-Lin Yan
A1 John H. Postlethwait
A1 Wenbiao Chen
A1 Han Wang
YR 2015
UL http://www.jneurosci.org/content/35/6/2572.abstract
AB Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder.