Genetic Modifiers of Neurotoxicity in a Drosophila Model of Parkinson’s Disease

Parkinson’s Disease (PD) is a neurological motor disorder that stems from the death of dopaminergic neurons in the substantia nigra, a region of the midbrain. In the United States, it is prevalent in 1% of people over 60 years of age. Rotenone is a compound that is known to induce PD-like symptoms via direct inhibition of Complex 1 in the mitochondria, leading to the formation of reactive oxygen species (ROS) and cell death in dopaminergic neurons. In Drosophila melanogaster, exposure to rotenone leads to locomotor impairments like those found in PD and has previously been used to model PD in flies. In this study, we used rotenone to induce PD-like symptoms in a subset of the Drosophila Genetic Reference Panel (DGRP) lines, which have known, unique polymorphisms. We assessed the effects of rotenone using a locomotive behavioral assay and compared DGRP lines to identify genetic variants that contribute to rotenone sensitivity. This means that a difference in assay performance can be attributed to the different genotype, so we can compare the polymorphisms between the fly lines and identify which mutation(s) may be responsible. We found 30 single nucleotide polymorphisms that are significantly associated with differential rotenone sensitivity, potentially providing insight into genetic factors associated with PD.