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Impact moléculaire de l’exposition subchronique par voie orale à un pesticide, le paraquat, dans un modèle murin transgénique de synucléinopathie humaine : implication du système nerveux entérique

Abstract : Parkinson's disease (PD) belongs to the a-synucleinopathies family. These pathologies have in common that they are linked to a-synuclein (a-syn), a neuronal protein whose precise roles are poorly defined. Some pesticides, such as paraquat, have been epidemiologically linked to the early onset of PD in farmers; some substances have become essential in the studies of synucleinopathies. Paraquat induces parkinsonian pathologies including a-syn aggregations or specific dopaminergic neurons loss. In our studies, we first set up a model of oral exposure to paraquat by drinking water. Subsequently, we studied the effects of this oral administration to paraquat on the enteric nervous system of the intestine of C57Bl/6 and TgM83 transgenic mice. This transgenic line has the peculiarity of simultaneously and spontaneously developing a synucleinopathy in the intestine and in the brain, displaying deposits of phosphorylated a-syn. The oral ingestion of paraquat induces acceleration in the appearance of enteric synucleinopathy. In a second biochemical study, we show that oral exposure to paraquat induces an overall increase in total a-syn levels in the central and enteric nervous systems of mice.Our results show the deleterious effects of paraquat oral administration on the intestine in relation to a-syn, by the acceleration of synucleinopathy but also by the induction of a widespread cerebral and enteric response, shown by an increase in cellular levels of a-syn
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https://tel.archives-ouvertes.fr/tel-01768310
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Submitted on : Tuesday, April 17, 2018 - 10:30:07 AM
Last modification on : Monday, October 21, 2019 - 4:34:18 PM

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Nicolas Naudet. Impact moléculaire de l’exposition subchronique par voie orale à un pesticide, le paraquat, dans un modèle murin transgénique de synucléinopathie humaine : implication du système nerveux entérique. Autre [q-bio.OT]. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1280⟩. ⟨tel-01768310⟩

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