Search

Your search keyword '"Davoust, Nathalie"' showing total 3 results
Start Over Author "Davoust, Nathalie" Topic paraquat
3 results on '"Davoust, Nathalie"'

1. Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila .

Author

Arsac JN, Sedru M, Dartiguelongue M, Vulin J, Davoust N, Baron T, and Mollereau B

Subjects
Animals, Brain drug effects, Brain metabolism, Disease Models, Animal, Dopaminergic Neurons drug effects, Dopaminergic Neurons metabolism, Drosophila metabolism, Herbicides toxicity, Male, Neurotoxins toxicity, Parkinson Disease metabolism, Drosophila drug effects, Paraquat toxicity, alpha-Synuclein metabolism
Abstract

Parkinson's disease (PD) is characterized by the progressive accumulation of neuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn) protein. The process of αSyn aggregation is induced during aging and enhanced by environmental stresses, such as the exposure to pesticides. Paraquat (PQ) is an herbicide which has been widely used in agriculture and associated with PD. PQ is known to cause an increased oxidative stress in exposed individuals but the consequences of such stress on αSyn conformation remains poorly understood. To study αSyn pathogenic modifications in response to PQ, we exposed Drosophila expressing human αSyn to a chronic PQ protocol. We first showed that PQ exposure and αSyn expression synergistically induced fly mortality. The exposure to PQ was also associated with increased levels of total and phosphorylated forms of αSyn in the Drosophila brain. Interestingly, PQ increased the detection of soluble αSyn in highly denaturating buffer but did not increase αSyn resistance to proteinase K digestion. These results suggest that PQ induces the accumulation of toxic soluble and misfolded forms of αSyn but that these toxic forms do not form fibrils or aggregates that are detected by the proteinase K assay. Collectively, our results demonstrate that Drosophila can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology.

Published
2021
Full Text
View/download PDF

2. Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity.

Author

Girard V, Goubard V, Querenet M, Seugnet L, Pays L, Nataf S, Dufourd E, Cluet D, Mollereau B, and Davoust N

Subjects
Animals, Drosophila Proteins genetics, Drosophila melanogaster drug effects, Drosophila melanogaster metabolism, Herbicides toxicity, Homeodomain Proteins genetics, Male, Neuroglia drug effects, Neuroglia metabolism, Parkinson Disease etiology, Parkinson Disease metabolism, Parkinson Disease pathology, RNA-Binding Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster growth & development, Gene Expression Regulation, Developmental, Homeodomain Proteins metabolism, Lipid Droplets chemistry, Neuroglia cytology, Paraquat toxicity, Parkinson Disease prevention & control, RNA-Binding Proteins metabolism
Abstract

Glial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD). Using a data-mining approach, we found that SPEN/SHARP is one of many astrocyte-expressed genes that are significantly differentially expressed in the substantia nigra of PD patients compared with control subjects. Interestingly, the differentially expressed genes are enriched in lipid metabolism-associated genes. In a Drosophila model of PD, we observed that flies carrying a loss-of-function allele of the ortholog split-ends (spen) or with glial cell-specific, but not neuronal-specific, spen knockdown were more sensitive to paraquat intoxication, indicating a protective role for Spen in glial cells. We also found that Spen is a positive regulator of Notch signaling in adult Drosophila glial cells. Moreover, Spen was required to limit abnormal accumulation of lipid droplets in glial cells in a manner independent of its regulation of Notch signaling. Taken together, our results demonstrate that Spen regulates lipid metabolism and storage in glial cells and contributes to glial cell-mediated neuroprotection.

Published
2020
Full Text
View/download PDF

3. Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity

Author

Girard, Victor, Goubard, Valérie, Querenet, Matthieu, Seugnet, Laurent, Pays, Laurent, Nataf, Serge, Dufourd, Eloïse, Cluet, David, Mollereau, Bertrand, Davoust, Nathalie, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Banque de tissus et de cellules [CHU - HCL] (Hôpital Edouard Herriot), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), SFR Biosciences, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), SFR Biosciences Projets Developpement Technologique Fondation Servier ENS Fond Recherche Fondation pour la Recherche Medicale French Ministry of Research and Education and Association France Parkinson, ANR-12-BSV1-0019,LipidinRetina,Dérégulation du métabolisme des lipides et conséquences sur la fonction et la survie des photorécépteurs: le rôle des gènes FATP chez la Drosophile et la souris(2012), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), ROSSI, Sabine, and BLANC - Dérégulation du métabolisme des lipides et conséquences sur la fonction et la survie des photorécépteurs: le rôle des gènes FATP chez la Drosophile et la souris - - LipidinRetina2012 - ANR-12-BSV1-0019 - BLANC - VALID

Subjects
Homeodomain Proteins, Male, Paraquat, Herbicides, Disease model, Parkinson's disease, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, Gene Expression Regulation, Developmental, RNA-Binding Proteins, Parkinson Disease, Lipid Droplets, Article, [SDV] Life Sciences [q-bio], Drosophila melanogaster, nervous system, Animals, Drosophila Proteins, lcsh:Q, lcsh:Science, Astrocyte, Neuroglia
Abstract

International audience; Glial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson's disease (PD). Using a data-mining approach, we found that SPEN/SHARP is one of many astrocyte-expressed genes that are significantly differentially expressed in the substantia nigra of PD patients compared with control subjects. Interestingly, the differentially expressed genes are enriched in lipid metabolism-associated genes. In a Drosophila model of PD, we observed that flies carrying a loss-of-function allele of the ortholog split-ends (spen) or with glial cell-specific, but not neuronal-specific, spen knockdown were more sensitive to paraquat intoxication, indicating a protective role for Spen in glial cells. We also found that Spen is a positive regulator of Notch signaling in adult Drosophila glial cells. Moreover, Spen was required to limit abnormal accumulation of lipid droplets in glial cells in a manner independent of its regulation of Notch signaling. Taken together, our results demonstrate that Spen regulates lipid metabolism and storage in glial cells and contributes to glial cell-mediated neuroprotection.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results