Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1785040602352582656 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10177284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT parralesmaciasvaleria thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT michelpatrickp thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT tourvilleaurore thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT raismanvozaririta thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT haikstephane thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT hunotstephane thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT bizatnicolas thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT lannuzelannie thepesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT parralesmaciasvaleria pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT michelpatrickp pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT tourvilleaurore pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT raismanvozaririta pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT haikstephane pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT hunotstephane pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT bizatnicolas pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms AT lannuzelannie pesticidechlordeconepromotesparkinsonismlikeneurodegenerationwithtaulesionsinmidbrainculturesandcelegansworms |