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 ␤ 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.

Abstract:We investigated the contribution of locomotor activity and learning and memory abilities to Alzheimer's disease induced by metal neurotoxicity. The metal neurotoxicity model was established by using locomotor activity tests and activity-avoidance conditioning paradigms, and observing changes in zebrafish behaviors after exposure to 50 µg/L of AlCl 3 with different pH values (pH 7.8, pH 6.8 and pH 5.8) for 24 hours and 96 hours. The results showed Alzheimer's disease-like behavior in locomotor activity tests and activity-avoidance conditioning paradigms by zebrafish receiving AlCl 3 in pH 5.8 significantly decreased compared to the control group and groups receiving AlCl 3 in pH 7.8 and pH 6.8 for 96 hours and 24 hours. These results provide evidences that exposure to AlCl 3 in an acid environment can influence locomotor activity and learning and memory abilities in zebrafish. In addition, exposure time and concentration of Al induced neurotoxicity and damaged the brain area of memory, resulting in Alzheimer's disease-like behavior.