Exposure to Mn/Zn ethylene-bis-dithiocarbamate and glyphosate pesticides leads to neurodegeneration in Caenorhabditis elegans

Abstract

Epidemiological evidence suggests positive correlations between pesticide usage and the incidence of Parkinson's disease (PD). To further explore this relationship, we used wild type (N2) Caenorhabditis elegans (C. elegans) to test the following hypothesis: Exposure to a glyphosate-containing herbicide (TD) and/or a manganese/zinc ethylene-bis-dithiocarbamate-containing fungicide (MZ) may lead to neurotoxicity. We exposed N2 worms to varying concentrations of TD or MZ for 30 min (acute) or 24 hours (chronic). To replicate agricultural usage, a third population was exposed to TD (acute) followed by MZ (acute). For acute TD exposure, the LC50 = 8.0% (r2: = 0.6890), while the chronic LC50 = 5.7% (r2 = 0.9433). Acute MZ exposure led to an LC50 = 0.22% (r2 = 0.5093), and chronic LC50 = 0.50% (r2 = 0.9733). The combined treatment for TD + MZ yielded an LC50 = 12.5% (r2 = 0.6367). Further studies in NW1229 worms, a pan-neuronally green fluorescent protein (GFP) tagged strain, indicated a statistically significant (p < 0.05) and dose-dependent reduction in green pixel number in neurons of treated worms following each paradigm. This reduction of pixel number was accompanied by visual neurodegeneration in photomicrographs. For the dual treatment, Bliss analysis suggested synergistic interactions. Taken together, these data suggest neuronal degeneration occurs in C. elegans following treatment with environmentally-relevant concentrations of TD or MZ.

Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

“…Impaired dopaminergic signaling in the substantia nigra is a key feature of Parkinson's disease, and Parkinson's risk has been associated with exposure to various pesticides, including the herbicide paraquat [238], although, to our knowledge, glyphosate has not yet been studied in this respect. However, exposure of C. elegans to glyphosate led to pathology in the nervous system in the region analogous to the nigrostriatal dopamine system associated with Parkinson's disease [239].…”

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].…”

The nematode Caenorhabditis elegans as an integrated toxicological tool to assess water quality and pollution

“…This aspect reinforces the concept that there must be other substances or chemicals in the water samples that were not detected a priori but even so exert weighty toxicological effects. Several reports showed that C. elegans was sensitive to different substances such as pesticides, heavy metals and toxins (Höss et al, 2013;Jiang et al, 2016;Lewis et al, 2013;Negga et al, 2011;Ruan et al, 2009;Yunhui et al, 2009). So it is possible that C. elegans toxicity could be explained by pollutants derived from the anthropogenic activities developed in the area (like agriculture, livestock and recreations).…”