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The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson’s disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key ch...

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Autores principales: Parrales-Macias, Valeria, Michel, Patrick P., Tourville, Aurore, Raisman-Vozari, Rita, Haïk, Stéphane, Hunot, Stéphane, Bizat, Nicolas, Lannuzel, Annie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177284/
https://www.ncbi.nlm.nih.gov/pubmed/37174736
http://dx.doi.org/10.3390/cells12091336
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author Parrales-Macias, Valeria
Michel, Patrick P.
Tourville, Aurore
Raisman-Vozari, Rita
Haïk, Stéphane
Hunot, Stéphane
Bizat, Nicolas
Lannuzel, Annie
author_facet Parrales-Macias, Valeria
Michel, Patrick P.
Tourville, Aurore
Raisman-Vozari, Rita
Haïk, Stéphane
Hunot, Stéphane
Bizat, Nicolas
Lannuzel, Annie
author_sort Parrales-Macias, Valeria
collection PubMed
description Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson’s disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.
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spelling pubmed-101772842023-05-13 The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms Parrales-Macias, Valeria Michel, Patrick P. Tourville, Aurore Raisman-Vozari, Rita Haïk, Stéphane Hunot, Stéphane Bizat, Nicolas Lannuzel, Annie Cells Article Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson’s disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD. MDPI 2023-05-07 /pmc/articles/PMC10177284/ /pubmed/37174736 http://dx.doi.org/10.3390/cells12091336 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parrales-Macias, Valeria
Michel, Patrick P.
Tourville, Aurore
Raisman-Vozari, Rita
Haïk, Stéphane
Hunot, Stéphane
Bizat, Nicolas
Lannuzel, Annie
The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title_full The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title_fullStr The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title_full_unstemmed The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title_short The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms
title_sort pesticide chlordecone promotes parkinsonism-like neurodegeneration with tau lesions in midbrain cultures and c. elegans worms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177284/
https://www.ncbi.nlm.nih.gov/pubmed/37174736
http://dx.doi.org/10.3390/cells12091336
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