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

التفاصيل البيبلوغرافية
العنوان: The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms.
المؤلفون: Parrales-Macias V; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Michel PP; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Tourville A; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Raisman-Vozari R; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Haïk S; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Hunot S; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France., Bizat N; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.; Faculté de Pharmacie de Paris, Université de Paris Cité, 75006 Paris, France., Lannuzel A; Paris Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.; Centre Hospitalier Universitaire de la Guadeloupe, Service de Neurologie, Faculté de Médecine de l'Université des Antilles, Centre d'Investigation Clinique (CIC) 1424, 97159 Pointe-à-Pitre, France.
المصدر: Cells [Cells] 2023 May 07; Vol. 12 (9). Date of Electronic Publication: 2023 May 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Chlordecone*/metabolism , Pesticides*/toxicity , Parkinsonian Disorders*/pathology , Parkinson Disease*/metabolism, Animals ; Humans ; Mice ; Caenorhabditis elegans/metabolism ; Ecosystem ; Dopaminergic Neurons/metabolism ; Mesencephalon/pathology
مستخلص: 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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فهرسة مساهمة: Keywords: Parkinsonism; cell culture model; chlordecone; dopamine neurons; neurodegeneration; tauopathy
المشرفين على المادة: RG5XJ88UDF (Chlordecone)
0 (Pesticides)
تواريخ الأحداث: Date Created: 20230513 Date Completed: 20230515 Latest Revision: 20230515
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10177284
DOI: 10.3390/cells12091336
PMID: 37174736
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells12091336