Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology

Masaki Ikeda, Takeshi Kawarabayashi, Yasuo Harigaya, Atsushi Sasaki, Shuichi Yamada, Etsuro Matsubara, Tetsuro Murakami, Yuya Tanaka, Tomoko Kurata, Xu Wuhua, Kenji Ueda, Hisashi Kuribara, Yasushi Ikarashi, Yoichi Nakazato, Koichi Okamoto, Koji Abe, Mikio Shoji

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Missense point mutations, duplication and triplication in the α-synuclein (αSYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of αSYN 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 αSYN pathologies, we generated TgαSYN transgenic mice overexpressing human αSYN with double mutations in A30P and A53T. Human αSYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble αSYN, as well as phosphorylated, ubiquitinated and nitrated αSYN, 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, TgαSYN is a useful model for analyzing the pathological cascade from aggregated αSYN to motor disturbance, and may be useful for drug trials.

Original languageEnglish
Pages (from-to)232-241
Number of pages10
JournalBrain Research
Volume1250
DOIs
Publication statusPublished - Jan 23 2009

Fingerprint

Synucleins
Transgenic Mice
Pathology
Parkinson Disease
Rotarod Performance Test
Lewy Bodies
Dopaminergic Neurons
Inclusion Bodies
Neurites
Substantia Nigra
Missense Mutation
Point Mutation
Dopamine
Neurons
Mutation

Keywords

  • α-synuclein
  • Mutation
  • Neurochemical
  • Parkinson's disease
  • Transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology. / Ikeda, Masaki; Kawarabayashi, Takeshi; Harigaya, Yasuo; Sasaki, Atsushi; Yamada, Shuichi; Matsubara, Etsuro; Murakami, Tetsuro; Tanaka, Yuya; Kurata, Tomoko; Wuhua, Xu; Ueda, Kenji; Kuribara, Hisashi; Ikarashi, Yasushi; Nakazato, Yoichi; Okamoto, Koichi; Abe, Koji; Shoji, Mikio.

In: Brain Research, Vol. 1250, 23.01.2009, p. 232-241.

Research output: Contribution to journalArticle

Ikeda, M, Kawarabayashi, T, Harigaya, Y, Sasaki, A, Yamada, S, Matsubara, E, Murakami, T, Tanaka, Y, Kurata, T, Wuhua, X, Ueda, K, Kuribara, H, Ikarashi, Y, Nakazato, Y, Okamoto, K, Abe, K & Shoji, M 2009, 'Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology', Brain Research, vol. 1250, pp. 232-241. https://doi.org/10.1016/j.brainres.2008.10.011
Ikeda, Masaki ; Kawarabayashi, Takeshi ; Harigaya, Yasuo ; Sasaki, Atsushi ; Yamada, Shuichi ; Matsubara, Etsuro ; Murakami, Tetsuro ; Tanaka, Yuya ; Kurata, Tomoko ; Wuhua, Xu ; Ueda, Kenji ; Kuribara, Hisashi ; Ikarashi, Yasushi ; Nakazato, Yoichi ; Okamoto, Koichi ; Abe, Koji ; Shoji, Mikio. / Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology. In: Brain Research. 2009 ; Vol. 1250. pp. 232-241.
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