Objective: The study aims to explore the role of melatonin receptor 1 (MT1) in the regulation of sleep-wake behavior in rotenone-induced Parkinson’s disease (PD) model in zebrafish.

Background: Sleep disorders are common in PD, which will aggravate the progress of the disease, and can cause the development of insomnia and daytime sleepiness. However, the specific mechanism of sleep-wake dysfunction in PD is still unclear. Melatonin and its receptor agonists can regulate the sleep-wake cycle and exert protective effects in various diseases.Sleep disorders are common in PD, which will aggravate the progress of the disease, and can cause the development of insomnia and daytime sleepiness. However, the specific mechanism of sleep-wake dysfunction in PD is still unclear. Melatonin and its receptor agonists can regulate the sleep-wake cycle and exert protective effects in various diseases.

Method: Rotenone was administered at 10 nM to zebrafish larvae from 72 hpf to 168 hpf to generate a PD zebrafish model. The motor behavior was examined after 4 days of rotenone treatment. Immunofluorescent staining and qRT-PCR were used to detect the dopaminergic neurons in zebrafish brains. The sleep-wake behavior was assessed using a zebrafish behavioral monitoring system at 48h. In situ hybridization was used to detect the expression of MT1 and melatonin receptor II. The ATP level in the tissue was detected by ATP detection kit.

Results: The results showed that rotenone induced motor dysfunction and abnormal sleep-wake behavior in zebrafish larvae. The zebrafish PD model exhibited shorter rest periods at night, more sleep-wake transitions, shorter sleep intervals, and more prolonged waking activity. In addition, the mRNA expression levels of mitochondrial oxidative stress and lipid-metabolism-related genes were changed in the PD zebrafish model. However, melatonin and its receptor agonist ramelteon could have protected against sleep-wake dysfunction by improving lipid metabolism disorder in the PD zebrafish model. This protective effect may have depended on MT1.

Conclusion: The rotenone-induced PD zebrafish model has sleep-wake behavior disorder, mitochondrial damage, and lipid metabolism disorder, and the MT1 expression level is decreased in the zebrafish model. Melatonin and MT1 agonist ramelteon pretreatment can improve lipid metabolism and sleep-wake behavior in PD zebrafish.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ramelteon-ameliorates-abnormal-sleep-wake-behavior-in-a-zebrafish-model-of-parkinsons-disease-by-facilitating-abnormal-lipid-metabolism/