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 hours) or acutely (30 min) exposed two Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC25, LC50 or LC75) of TouchDown® (TD) as per cent active ingredient (glyphosate), or Mancozeb® (MZ) as per cent 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.

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

“…Oxidative stress also resulted in the neurodegeneration of dopaminergic (DAergic) neurons, indicated by the fact that treated worms showed a significant decrease in DA concentration compared to untreated worms [143]. Similar neurodegeneration has been shown following exposure to mancozeb [144,145].…”

“…Manganese-containing dithiocarbamate fungicides, such as maneb and mancozeb, have been researched heavily due to their neurotoxicity [143][144][145]. Manganese exposure by itself has been shown to result in a variety of detrimental effects in C. elegans [146][147][148].…”

Nutrition-dependent GABA deficiencies in endocrine pancreas causes cancer as shown for betel nut consumers and for diets with low vitamin B6

“…The synthesis of GABA should then decrease in relation to this intrinsic property of maize-at least when maize becomes the major diet. Moreover, it has been observed that glyphosate itself alters GABA ergic neurons 15 . A maize diet leads to pellagra provoked by niacin deficiency; an associated vitamin B 6 loss should also elicit neurological troubles, dementia or epilepsy, as GABA is a major transmitter in the central nervous system.…”

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

“…Its mode of action is to interfere with the synthesis of phenylalanine, tyrosine and tryptophan. There have been a few human case studies possibly linking glyphosate exposure to Parkinsonism, and it has been reported that glyphosate exposure could result in not only dopaminergic but also GABAergic neurodegeneration in C. elegans (Gui et al, 2012;Negga et al, 2011;Negga et al, 2012). In vitro studies have reported glyphosate-induced cell death via apoptosis and autophagy, but glyphosate exposure did not increase alpha-synuclein levels in vitro (Chorfa et al, 2013;Chorfa et al, 2014;Gui et al, 2012).…”