title: Prion-like acceleration of a synucleinopathy in a transgenic mouse model.
abstract: Our aim in this study was to investigate experimentally the possible in vivo transmission of a synucleinopathy, using a transgenic mouse model (TgM83) expressing the human A53T mutated α-synuclein. Brain homogenates from old TgM83 mice showing motor clinical signs due to the synucleinopathy and containing insoluble and phosphorylated (pSer129) α-synuclein were intracerebrally inoculated in young TgM83 mice. This triggered an early onset of characteristic motor clinical signs, compared with uninoculated TgM83 mice or to mice inoculated with a brain homogenate from a young, healthy TgM83 mouse. This early disease was associated with insoluble α-synuclein phosphorylated on Ser129, as already identified in old and sick uninoculated TgM83 transgenic mice. Although the molecular mechanisms remain to be determined, acceleration of the pathology following inoculation of mice expressing human mutated α-synuclein with tissues from mice affected by the synucleinopathy, could be consistent with "prion-like" propagation of the disease.
authors.affiliation: Anses, Laboratoire de Lyon, Unité Maladies Neurodégénératives, Lyon, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Mougenot
authors.forename: Simon
authors.initials: S
authors.lastname: Nicot
authors.forename: Anna
authors.initials: A
authors.lastname: Bencsik
authors.forename: Eric
authors.initials: E
authors.lastname: Morignat
authors.forename: Jérémy
authors.initials: J
authors.lastname: Verchère
authors.forename: Latefa
authors.initials: L
authors.lastname: Lakhdar
authors.forename: Stéphane
authors.initials: S
authors.lastname: Legastelois
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D017096:Prion Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D012694:Serine / Q000235:genetics; D016019:Survival Analysis
chemical_list: D007381:Intermediate Filament Proteins; C430456:desmuslin; D012694:Serine