Environmental Toxins Trigger PD-like Progression Via Increased Alpha-synuclein Release from Enteric Neurons in Mice

Overview

Journal Sci Rep

Specialty Science

Date 2012 Dec 4

PMID 23205266

Citations 193

Authors

Francisco Pan-Montojo

Mathias Schwarz

Clemens Winkler

Mike Arnhold

Gregory A OSullivan

Arun Pal

Jonas Said

Giovanni Marsico

Jean-Marc Verbavatz

Margarita Rodrigo-Angulo

Gabriele Gille

Richard H W Funk

Heinz Reichmann

Affiliations

Soon will be listed here.

Abstract

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.

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