title: Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice.
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.
authors.affiliation: Institute for Anatomy, TU-Dresden , Fetscherstr. 74, 01307, Dresden, Germany. Francisco_Jose.Pan-Montojo@tu-dresden.de
authors.forename: Francisco
authors.initials: F
authors.lastname: Pan-Montojo
authors.forename: Mathias
authors.initials: M
authors.lastname: Schwarz
authors.forename: Clemens
authors.initials: C
authors.lastname: Winkler
authors.forename: Mike
authors.initials: M
authors.lastname: Arnhold
authors.forename: Gregory A
authors.initials: GA
authors.lastname: O'Sullivan
authors.forename: Arun
authors.initials: A
authors.lastname: Pal
authors.forename: Jonas
authors.initials: J
authors.lastname: Said
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsico
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Verbavatz
authors.forename: Margarita
authors.initials: M
authors.lastname: Rodrigo-Angulo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gille
authors.forename: Richard H W
authors.initials: RH
authors.lastname: Funk
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017615:Enteric Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D012402:Rotenone / Q000633:toxicity*; D013562:Sympathectomy; D014628:Vagotomy; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D007306:Insecticides; D051844:alpha-Synuclein; D012402:Rotenone