The Drosophila vesicular monoamine transporter reduces pesticide-induced loss of dopaminergic neurons.
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.
Lawal
Hakeem O
HO
Department of Psychiatry and Biobehavioral Sciences, Gonda Center for Neuroscience and Genetics Research, David Geffen School of Medicine at University of California, Los Angeles, California, USA.
Chang
Hui-Yun
HY
Terrell
Ashley N
AN
Brooks
Elizabeth S
ES
Pulido
Dianne
D
Simon
Anne F
AF
Krantz
David E
DE
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010575:Pesticides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D050493:Vesicular Monoamine Transport Proteins / Q000502:physiology*
D006133:Growth Substances; D010575:Pesticides; D050493:Vesicular Monoamine Transport Proteins; D004298:Dopamine
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