Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice
| Autor: | Gregory A. O'Sullivan, Mathias Schwarz, Heinz Reichmann, M.L. Rodrigo-Angulo, Francisco J Pan-Montojo, Arun Pal, Clemens Winkler, Jean-Marc Verbavatz, Gabriele Gille, Jonas Said, Giovanni Marsico, Mike Arnhold, Richard Funk |
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| Přispěvatelé: | UAM. Departamento de Anatomía, Histología y Neurociencia |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Insecticides Neurite Medicina Central nervous system Primary Cell Culture Biology Vagotomy medicine.disease_cause Axonal Transport Enteric Nervous System Article chemistry.chemical_compound Mice Rotenone medicine Animals Humans ddc:610 Parkinson Disease Secondary Sympathectomy Alpha-synuclein Neurons Desease of nervous system Multidisciplinary Toxin Brain biology geneitcs parkinson Olfactory bulb Experimental models of disease medicine.anatomical_structure Parkinson's desease chemistry nervous system Axoplasmic transport Degeneration alpha-Synuclein Enteric nervous system Neuroscience Biologie Genetik Parkinson |
| Zdroj: | Scientific Reports Biblos-e Archivo. Repositorio Institucional de la UAM instname |
| ISSN: | 2045-2322 |
| Popis: | Pathological studies on Parkinson’s disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD This work was supported by the Fritz-Thyssen Foundation, theGerman Parkinson’s disease Society and by Amelia Jimenez Gomez as private donor |
| Databáze: | OpenAIRE |
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