The Drosophila vesicular monoamine transporter reduces pesticide-induced loss of dopaminergic neurons

• Published in: Neurobiology of disease Vol. 40; no. 1; pp. 102 - 112
• Main Authors: Lawal, Hakeem O., Chang, Hui-Yun, Terrell, Ashley N., Brooks, Elizabeth S., Pulido, Dianne, Simon, Anne F., Krantz, David E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2010; Elsevier
• Subjects: Animals; Cell Death - drug effects; Cell Death - physiology; Cell Survival - drug effects; Cell Survival - physiology; Disease Models, Animal; Dopamine; Dopamine - physiology; Down-Regulation - drug effects; Down-Regulation - physiology; Drosophila; Drosophila melanogaster - drug effects; Drosophila melanogaster - physiology; Growth Substances - genetics; Growth Substances - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Parkinson's disease; Pesticides - antagonists & inhibitors; Pesticides - toxicity; Vesicular Monoamine Transport Proteins - physiology; Vesicular transporter; VMAT; VMAT; Dopamine; Parkinson's disease; Vesicular transporter; Drosophila
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2010.05.008

Dopamine is cytotoxic and may play a role in the development of Parkinson's disease. However, its interaction with environmental risk factors such as pesticides remains poorly understood. The vesicular monoamine transporter (VMAT) regulates intracellular dopamine content, and we have tested the neuroprotective effects of VMAT in vivo using the model organism Drosophila melanogaster. We find that Drosophila VMAT ( dVMAT) mutants contain fewer dopaminergic neurons than wild type, consistent with a developmental effect, and that dopaminergic cell loss in the mutant is exacerbated by the pesticides rotenone and paraquat. Overexpression of DVMAT protein does not increase the survival of animals exposed to rotenone, but blocks the loss of dopaminergic neurons caused by this pesticide. These results are the first to demonstrate an interaction between a VMAT and pesticides in vivo, and provide an important model to investigate the mechanisms by which pesticides and cellular DA may interact to kill dopaminergic cells.