A new Drosophila model to study the interaction between genetic and environmental factors in Parkinson's disease

The fruit fly Drosophila melanogaster has long been used as a model organism for human diseases, including Parkinson׳s disease (PD). Its short lifespan, simple maintenance, and the widespread availability of genetic tools allow researchers to study disease mechanisms as well as potential drug therapies. Many different PD models have already been developed, including ones utilizing mutated α-Syn and chronic exposure to rotenone. However, few animal models have been used to study interaction between the PD causing factors. In this study, we developed a new model of PD for use in the larval stage in order to study interaction between genetic and environmental factors. First, the 3rd instar larvae (90-94 hours after egg laying) expressing a mutated form of human α-Syn (A53T) in dopaminergic (DA) neurons were video-taped and quantified for locomotion (e.g. crawling pattern and speed) using ImageJ software. A53T mutant larvae showed locomotion deficits and also loss of DA neurons in age-dependent manner. Similarly, larvae chronically exposed to rotenone (10 μM in food) showed age-dependent decline in locomotion accompanied by loss of DA neurons. We further show that combining the two models, by exposing A53T mutant larvae to rotenone, causes a much more severe PD phenotype (i.e. locomotor deficit). Our finding shows interaction between genetic and environmental factors underlying development of PD symptoms. This model can be used to further study mechanisms underlying the interaction between genes and different environmental PD factors, as well as to explore potential therapies for PD treatment.