Natural Sciences Research Seminar Series - Dr. Hakeem Lawal: UCLA Neuropsychiatric Institute

Using Drosophila melanogaster to Test Gene-environment Interactions Relevant to Parkinson's Disease

Using Drosophila melanogaster to test gene-environment interactions relevant to Parkinson's disease ABSTRACT A pathological hallmark of Parkinson’s disease is the loss of dopaminergic neurons. Indeed, dysregulation of dopamine has been proposed as a causal factor in the disease, although the underlying mechanisms are not known. Several genetic factors for PD have been identified including mutations in the human gene parkin. Exposure to environmental toxins also increases the risk of PD. Using Drosophila, we are investigating the regulation of dopamine transport and susceptibility of DA neurons to toxicity produced by pesticides. The Vesicular Monoamine Transporter (VMAT) is a twelve transmembrane domain protein that packages and transports dopamine and serotonin into synaptic vesicles for exocytosis. We have previously shown that over-expresssion of Drosophila VMAT (DVMAT) decreases the neurotoxic effects of a human parkin mutant. Here the goal is to understand the interaction between environmental toxins such as rotenone and paraquat, and the aminergic pathway in a genetically tractable organism. We report a differential effect of VMAT over-expression in the rescue of neurotoxicity induced by rotenone compared to paraquat. These data highlight a possible mechanistic difference between how pesticides such as paraquat and rotenone with cellular dopamine.