title: Exposure to glyphosate- and/or Mn/Zn-ethylene-bis-dithiocarbamate-containing pesticides leads to degeneration of γ-aminobutyric acid and dopamine neurons in Caenorhabditis elegans.
abstract: Previous studies demonstrate a positive correlation between pesticide usage and Parkinson's disease (PD), which preferentially targets dopaminergic (DAergic) neurons. In order to examine the potential relationship between two common pesticides and specific neurodegeneration, we chronically (24 h) or acutely (30 min) exposed two Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC(25), LC(50) or LC(75)) of TouchDown(®) (TD) as percent active ingredient (glyphosate), or Mancozeb(®) (MZ) as percent active ingredient (manganese/zinc ethylene-bis-dithiocarbamate). Furthermore, to more precisely model environmental exposure, worms were also exposed to TD for 30 min, followed by 30-min incubation with varying MZ concentrations. Previous data from out lab suggested general neuronal degeneration using the worm strain NW1229 (pan-neuronal//green fluorescent protein (GFP) construct). To determine whether distinct neuronal groups were preferentially affected, we specifically used EG1285 (GABAergic neurons//GFP construct) and BZ555 (DAergic neurons//GFP construct) worms to verify GABAergic and DAergic neurodegeneration, respectively. Results indicated a statistically significant decrease, when compared to controls (CN), in number of green pixels associated with GABAergic neurons in both chronic (*P < 0.05) and acute (*P < 0.05) treatment paradigms. Analysis of the BZ555 worms indicated a statistically significant decrease (*P < 0.05) in number of green pixels associated with DAergic neurons in both treatment paradigms (chronic and acute) when compared to CN. Taken together, our data suggest that exposure to TD and/or MZ promotes neurodegeneration in both GABAergic and DAergic neurons in the model organism C. elegans.
authors.affiliation: Department of Biology, King College, 1350 King College Road, Bristol, TN 37620, USA.
authors.forename: Rekek
authors.initials: R
authors.lastname: Negga
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Stuart
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Machen
authors.forename: Joel
authors.initials: J
authors.lastname: Salva
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lizek
authors.forename: S Jayne
authors.initials: SJ
authors.lastname: Richardson
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Osborne
authors.forename: Oriol
authors.initials: O
authors.lastname: Mirallas
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: McVey
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Fitsanakis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005659:Fungicides, Industrial / Q000633:toxicity; D059330:GABAergic Neurons / Q000187:drug effects* / Q000473:pathology; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000187:drug effects / Q000473:pathology; D008344:Maneb / Q000633:toxicity*; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D015038:Zineb / Q000633:toxicity*; D000097797:Glyphosate
chemical_list: D005659:Fungicides, Industrial; D005998:Glycine; D049452:Green Fluorescent Proteins; D008344:Maneb; D009943:Organophosphorus Compounds; D010575:Pesticides; D015038:Zineb; D000097797:Glyphosate; C404484:N-(phosphonomethyl)glycine trimethylsulfonium salt; C013099:mancozeb