title: Motor impairment and aberrant production of neurochemicals in human alpha-synuclein A30P+A53T transgenic mice with alpha-synuclein pathology.
abstract: Missense point mutations, duplication and triplication in the alpha-synuclein (alphaSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of alphaSYN pathologies, e.g., Lewy bodies (LBs) and Lewy neurites (LNs), and a loss of dopaminergic neurons in the substantia nigra that leads to motor disturbances. To elucidate the mechanism of alphaSYN pathologies, we generated TgalphaSYN transgenic mice overexpressing human alphaSYN with double mutations in A30P and A53T. Human alphaSYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble alphaSYN, as well as phosphorylated, ubiquitinated and nitrated alphaSYN, was accumulated in the brains. Significantly decreased levels of dopamine (DA) were recognized in the striatum. Motor impairment was revealed in a rotarod test. Thus, TgalphaSYN is a useful model for analyzing the pathological cascade from aggregated alphaSYN to motor disturbance, and may be useful for drug trials.
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Harigaya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Xu
authors.initials: X
authors.lastname: Wuhua
authors.forename: Kenji
authors.initials: K
authors.lastname: Ueda
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kuribara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045442:Rotarod Performance Test; D012701:Serotonin / Q000378:metabolism; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D051844:alpha-Synuclein; D012701:Serotonin; D000109:Acetylcholine; D004298:Dopamine