Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson’s Disease

 Meng‑Zhu Pang1,2 · Han‑Xing Li1  · Xue‑Qin Dai2  · Xiao‑Bo Wang2  · Jun‑Yi Liu3  · Yun Shen1  · Xing Xu1  · Zhao‑Min Zhong4,5 · Han Wang4,5 · Chun‑Feng Liu1,2,6  · Fen Wang1,2
1 Department of Neurology and Clinical Research Center of Neurological Disease, The Second Afliated Hospital of Soochow University, Suzhou 215004, China 
2 Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institutes of Neuroscience, Soochow University, Suzhou 215123, China 
3 Department of Neurology, The Fourth Afliated Hospital of Soochow University, Suzhou 215000, China 
4 Center for Circadian Clocks, Soochow University, Suzhou 215123, China 
5 School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China 
6 Department of Neurology, Xiongan Xuanwu Hospital, Xiongan 071700, China

Abstract
Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.

Keywords
Zebrafsh; Melatonin; Melatonin receptor 1; Parkinson’s disease; Sleep-wake disorder; Lipid metabolism