Early motor deficits, sleep dysfunction and reduction in dopaminergic neurons in a park7 -/- zebrafish larval model of Parkinson’s disease

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Abstract Parkinson's Disease (PD) is the fastest-growing neurological disorder and only symptomatic treatment is available. Zebrafish are ideally suited for high-throughput screening of disease modifying drugs and mechanistic studies. Mutations in park7 are associated with early-onset familial PD. Additionally, altered levels and subcellular location of the park7 protein product (DJ-1) have been found in PD patients without known park7 mutations. Here, we show that larval park7 −/− zebrafish show reduced number of dopaminergic neurons and motor dysfunction, similarly to the 1-methyl-4-phenylpyridinium (MPP + )-induced PD model. Additionally, PD-associated prodromal symptoms, such as reduced sensory function, increased sleep latency and daytime sleepiness, were also observed in the park7 −/− , but not in the MPP + -induced PD model. The park7 −/− is the first stable genetic zebrafish model of Parkinson’s disease which shows both motor and non-motor symptoms, together with a reduction in dopaminergic neurons, at a larval stage. The model should therefore be highly valuable as a tool for PD related drug screening and mechanistic studies.

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