Early motor deficits, sleep dysfunction and reduction in dopaminergic neurons in a PARK7-/- zebrafish larval model of Parkinson’s disease

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, however also idiopathic PD patients without known mutations in PARK7 show altered subcellular location and levels of its protein product DJ-1 in pathological tissues. Here, we show that PARK7-/- zebrafish already at their larval stage show a correlation between reduced number of dopaminergic neurons and motor dysfunction. Additionally, PD associated prodromal symptoms as reduced sensory function, increased sleep latency and light phase sleepiness were also observed. The 1-methyl-4-phenylpyridinium (MPP+) exposed PD model did not reproduce similar sleep disturbances. This is the first stable genetic larval zebrafish model of Parkinson’s disease which shows both motor and non-motor symptoms together with a reduction in dopaminergic neurons. The model should therefore be highly valuable as a tool for PD related drug screening and mechanistic studies.