title: Transmission of prion strains in a transgenic mouse model overexpressing human A53T mutated α-synuclein.
abstract: There is a growing interest in the potential roles of misfolded protein interactions in neurodegeneration. To investigate this issue, we inoculated 3 prion strains intracerebrally into transgenic (TgM83) mice that overexpress human A53T α-synuclein. In comparison to nontransgenic controls, there was a striking decrease in the incubation periods of scrapie, classic and H-type bovine spongiform encephalopathies(C-BSE and H-BSE), with conservation of the histopathologic and biochemical features characterizing these 3 prion strains. TgM83 mice died of scrapie or C-BSE prion diseases before accumulating the insoluble and phosphorylated forms of α-synuclein specific to late stages of synucleinopathy. In contrast, the median incubation time for TgM83 mice inoculated with H-BSE was comparable to that observed when these mice were uninfected, thereby allowing the development of molecular alterations of α-synuclein. The last 4 mice of this cohort exhibited early accumulations of H-BSE prion protein along with α-synuclein pathology. The results indicate that a prion disease was triggered concomitantly with an overt synucleinopathy in some transgenic mice overexpressing human A53T α-synuclein after intracerebral inoculation with an H-BSE prion strain.
authors.affiliation: Agence Nationale de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail - ANSES, Lyon, France.
authors.forename: Anne-Laure J
authors.initials: AL
authors.lastname: Mougenot
authors.forename: Anna
authors.initials: A
authors.lastname: Bencsik
authors.forename: Simon
authors.initials: S
authors.lastname: Nicot
authors.forename: Johann
authors.initials: J
authors.lastname: Vulin
authors.forename: Eric
authors.initials: E
authors.lastname: Morignat
authors.forename: Jérémy
authors.initials: J
authors.lastname: Verchère
authors.forename: Dominique
authors.initials: D
authors.lastname: Bétemps
authors.forename: Latefa
authors.initials: L
authors.lastname: Lakhdar
authors.forename: Stéphane
authors.initials: S
authors.lastname: Legastelois
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Baron
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000473:pathology* / Q000635:transmission; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D012608:Scrapie / Q000235:genetics / Q000473:pathology* / Q000635:transmission; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D011328:Prions; D051844:alpha-Synuclein