Dopaminergic neurotoxicity of S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, and S-methyl-N,N-diethylthiocarbamate (MeDETC) in Caenorhabditis elegans

Samuel W. Caito, William M. Valentine, Michael Aschner

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Epidemiological studies corroborate a correlation between pesticide use and Parkinson's disease (PD). Thiocarbamate and dithiocarbamate pesticides are widely used and produce neurotoxicity in the peripheral nervous system. Recent evidence from rodent studies suggests that these compounds also cause dopaminergic (DAergic) dysfunction and altered protein processing, two hallmarks of PD. However, DAergic neurotoxicity has yet to be documented. We assessed DAergic dysfunction in Caenorhabditis elegans (C. elegans) to investigate the ability of thiocarbamate pesticides to induce DAergic neurodegeneration. Acute treatment with either S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, or a common reactive intermediate of dithiocarbamate and thiocarbamate metabolism, S-methyl-N,N-diethylthiocarbamate (MeDETC), to gradual loss of DAergic cell morphology and structure over the course of 6 days in worms expressing green fluorescent protein (GFP) under a DAergic cell specific promoter. HPLC analysis revealed decreased DA content in the worms immediately following exposure to MeDETC, EPTC, and molinate. In addition, worms treated with the three test compounds showed a drastic loss of DAergic-dependent behavior over a time course similar to changes in DAergic cell morphology. Alterations in the DAergic system were specific, as loss of cell structure and neurotransmitter content was not observed in cholinergic, glutamatergic, or GABAergic systems. Overall, our data suggest that thiocarbamate pesticides promote neurodegeneration and DAergic cell dysfunction in C. elegans, and may be an environmental risk factor for PD. A correlation exists between pesticide use and Parkinson's disease. We investigated the ability of thiocarbamate pesticides to induce dopaminergic neurodegeneration in Caenorhabditis elegans. Treatment with thiocarbamates led to selective loss of dopaminergic cell morphology, and decreased dopamine content and dopaminergic-dependent behavior. Our data suggest that thiocarbamate pesticides may be environmental risk factors for Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)837-851
Number of pages15
JournalJournal of Neurochemistry
Volume127
Issue number6
DOIs
StatePublished - Dec 2013
Externally publishedYes

Fingerprint

Thiocarbamates
Caenorhabditis elegans
Pesticides
Parkinson Disease
Aptitude
Peripheral Nervous System
Neurology
Green Fluorescent Proteins
EPTC
molinate
Metabolism
Cholinergic Agents
Neurotransmitter Agents
Epidemiologic Studies
Rodentia
Dopamine
High Pressure Liquid Chromatography

Keywords

  • C. elegans
  • dopamine
  • EPTC
  • molinate
  • neurodegeneration
  • pesticide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Dopaminergic neurotoxicity of S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, and S-methyl-N,N-diethylthiocarbamate (MeDETC) in Caenorhabditis elegans. / Caito, Samuel W.; Valentine, William M.; Aschner, Michael.

In: Journal of Neurochemistry, Vol. 127, No. 6, 12.2013, p. 837-851.

Research output: Contribution to journalArticle

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abstract = "Epidemiological studies corroborate a correlation between pesticide use and Parkinson's disease (PD). Thiocarbamate and dithiocarbamate pesticides are widely used and produce neurotoxicity in the peripheral nervous system. Recent evidence from rodent studies suggests that these compounds also cause dopaminergic (DAergic) dysfunction and altered protein processing, two hallmarks of PD. However, DAergic neurotoxicity has yet to be documented. We assessed DAergic dysfunction in Caenorhabditis elegans (C. elegans) to investigate the ability of thiocarbamate pesticides to induce DAergic neurodegeneration. Acute treatment with either S-ethyl N,N-dipropylthiocarbamate (EPTC), molinate, or a common reactive intermediate of dithiocarbamate and thiocarbamate metabolism, S-methyl-N,N-diethylthiocarbamate (MeDETC), to gradual loss of DAergic cell morphology and structure over the course of 6 days in worms expressing green fluorescent protein (GFP) under a DAergic cell specific promoter. HPLC analysis revealed decreased DA content in the worms immediately following exposure to MeDETC, EPTC, and molinate. In addition, worms treated with the three test compounds showed a drastic loss of DAergic-dependent behavior over a time course similar to changes in DAergic cell morphology. Alterations in the DAergic system were specific, as loss of cell structure and neurotransmitter content was not observed in cholinergic, glutamatergic, or GABAergic systems. Overall, our data suggest that thiocarbamate pesticides promote neurodegeneration and DAergic cell dysfunction in C. elegans, and may be an environmental risk factor for PD. A correlation exists between pesticide use and Parkinson's disease. We investigated the ability of thiocarbamate pesticides to induce dopaminergic neurodegeneration in Caenorhabditis elegans. Treatment with thiocarbamates led to selective loss of dopaminergic cell morphology, and decreased dopamine content and dopaminergic-dependent behavior. Our data suggest that thiocarbamate pesticides may be environmental risk factors for Parkinson's disease.",
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