Modelling Organophosphate Intoxication in C. Elegans Highlights Nicotinic Acetylcholine Receptor Determinants That Mitigate Poisoning

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2023 Apr 21

PMID 37083685

Authors

Patricia G Izquierdo

Claude L Charvet

Cedric Neveu

A Christopher Green

John E H Tattersall

Lindy Holden-Dye

Vincent OConnor

Affiliations

Soon will be listed here.

Abstract

Organophosphate intoxication via acetylcholinesterase inhibition executes neurotoxicity via hyper stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans and use its impact on pharyngeal pumping as a bio-assay to model poisoning through these neurotoxins. This assay provides a tractable measure of acetylcholine receptor mediated contraction of body wall muscle. Investigation of the time dependence of organophosphate treatment and the genetic determinants of the drug-induced inhibition of pumping highlight mitigating modulation of the effects of paraoxon-ethyl. We identified mutants that reduce acetylcholine receptor function protect against the consequence of intoxication by organophosphates. Data suggests that reorganization of cholinergic signalling is associated with organophosphate poisoning. This reinforces the under investigated potential of using therapeutic approaches which target a modulation of nicotinic acetylcholine receptor function to treat the poisoning effects of this important class of neurotoxins.

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