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

Hakeem O. Lawal; Hui-Yun Chang; Ashley N. Terrell; Elizabeth S. Brooks; Dianne Pulido; Anne F. Simon; David E. Krantz

Neurobiology of Disease (Oct 2010)

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

Hakeem O. Lawal,
Hui-Yun Chang,
Ashley N. Terrell,
Elizabeth S. Brooks,
Dianne Pulido,
Anne F. Simon,
David E. Krantz

Affiliations

Hakeem O. Lawal: 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
Hui-Yun Chang: 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
Ashley N. Terrell: 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
Elizabeth S. Brooks: 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
Dianne Pulido: 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
Anne F. Simon: 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
David E. Krantz: Corresponding author. Fax: +1 310 206 9877.; 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

Journal volume & issue: Vol. 40, no. 1
pp. 102 – 112

Abstract

Read online

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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords