Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning.
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 neuro...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0284786 |
| _version_ | 1797829885772693504 |
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| author | Patricia G Izquierdo Claude L Charvet Cedric Neveu A Christopher Green John E H Tattersall Lindy Holden-Dye Vincent O'Connor |
| author_facet | Patricia G Izquierdo Claude L Charvet Cedric Neveu A Christopher Green John E H Tattersall Lindy Holden-Dye Vincent O'Connor |
| author_sort | Patricia G Izquierdo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T13:28:28Z |
| format | Article |
| id | doaj.art-4f9d60c94fb44e47b32f26d841109694 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T13:28:28Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4f9d60c94fb44e47b32f26d8411096942023-05-10T05:31:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01184e028478610.1371/journal.pone.0284786Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning.Patricia G IzquierdoClaude L CharvetCedric NeveuA Christopher GreenJohn E H TattersallLindy Holden-DyeVincent O'ConnorOrganophosphate 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.https://doi.org/10.1371/journal.pone.0284786 |
| spellingShingle | Patricia G Izquierdo Claude L Charvet Cedric Neveu A Christopher Green John E H Tattersall Lindy Holden-Dye Vincent O'Connor Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. PLoS ONE |
| title | Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. |
| title_full | Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. |
| title_fullStr | Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. |
| title_full_unstemmed | Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. |
| title_short | Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning. |
| title_sort | modelling organophosphate intoxication in c elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning |
| url | https://doi.org/10.1371/journal.pone.0284786 |
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