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Título: | Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates |
Fecha de publicación: | 7-may-2020 |
Editorial: | Oxford University Press |
Cita bibliográfica: | Brain Journal of Neurology n.143; año 2020 1462–1475 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina |
Palabras clave: | Parkinson disease a-synuclein Neurodegeneration gut Monkey |
Resumen: | In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of a-synucleincontaining Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived a-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of a-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that a-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of a-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous a-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease. |
Autor/es principal/es: | Herrero Ezquerro, María Trinidad Arotcarena, Marie-Laure Dovero, Sandra Prigent, Alice Bourdenx, Mathieu Camus, Sandrine Porras, Gregory Thiolat, Marie-Laure Tasselli, Maddalena Aubert, Philippe Kruse, Niels Mollenhauer, Brit Trigo Damas, Ines Estrada, Cristina Garcia-Carrillo, Nuria Vaikath, Nishant El-Agnaf, Omar M.A. Vila, Miquel Obeso, Jose A. Derkinderen, Pascal Dehay, Benjamin Bezard, Erwan |
Versión del editor: | https://academic.oup.com/brain/article/143/5/1462/5831949?login=true |
URI: | http://hdl.handle.net/10201/139130 |
DOI: | http//:doi:10.1093/brain/awaa096 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 14 |
Derechos: | info:eu-repo/semantics/openAccess |
Descripción: | ©<2020>. This manuscript version is made available under the CC POR 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Submitted, Accepted, Published, version of a Published Work that appeared in final form in Brain Journal of Neurology . To access the final edited and published work see https://doi:10.1093/brain/awaa096 |
Aparece en las colecciones: | Artículos: Anatomía Humana y Psicobiología |
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