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Recruitment of calbindin into nigral dopamine neurons protects against MPTP-Induced parkinsonism.
https://repo.qst.go.jp/records/49156
https://repo.qst.go.jp/records/491564cad573d-14c3-4bc5-832e-e36c622c0d4c
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-09-03 | |||||
タイトル | ||||||
タイトル | Recruitment of calbindin into nigral dopamine neurons protects against MPTP-Induced parkinsonism. | |||||
言語 | ||||||
言語 | eng | |||||
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資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Ken-ichi, Inoue
× Ken-ichi, Inoue× Miyachi, Shigehiro× Nishi, Katsunori× Okado, Haruo× Nagai, Yuji× Mainamimoto, Takafumi× Nambu, Atsushi× Takada, Masahiko× Nagai, Yuji× Minamimoto, Takafumi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | BACKGROUND: Parkinson's disease is caused by dopamine deficiency in the striatum, which is a result of loss of dopamine neurons from the substantia nigra pars compacta. There is a consensus that a subpopulation of nigral dopamine neurons that expresses the calcium-binding protein calbindin is selectively invulnerable to parkinsonian insults. The objective of the present study was to test the hypothesis that dopamine neuron degeneration might be prevented by viral vector-mediated gene delivery of calbindin into the dopamine neurons that do not normally contain it. METHODS: A calbindin-expressing adenoviral vector was injected into the striatum of macaque monkeys to be conveyed to cell bodies of nigral dopamine neurons through retrograde axonal transport, or the calbindin-expressing lentiviral vector was injected into the nigra directly because of its predominant uptake from cell bodies and dendrites. The animals in which calbindin was successfully recruited into nigral dopamine neurons were administered systemically with MPTP. RESULTS: In the monkeys that had received unilateral vector injections, parkinsonian motor deficits, such as muscular rigidity and akinesia/bradykinesia, appeared predominantly in the limbs corresponding to the non-calbindin-recruited hemisphere after MPTP administration. Data obtained from tyrosine hydroxylase immunostaining and PET imaging for the dopamine transporter revealed that the nigrostriatal dopamine system was preserved better on the calbindin-recruited side. Conversely, on the non-calbindin-recruited control side, many more dopamine neurons expressed α-synuclein. CONCLUSIONS: The present results indicate that calbindin recruitment into nigral dopamine neurons protects against the onset of parkinsonian insults, thus providing a novel approach to PD prevention. |
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書誌情報 |
Movement Disorders 巻 34, 号 2, p. 200-209, 発行日 2018-08 |
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出版者 | ||||||
出版者 | Wiley | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0885-3185 | |||||
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識別子タイプ | PMID | |||||
関連識別子 | 30161282 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1002/mds.107 | |||||
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識別子タイプ | URI | |||||
関連識別子 | https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.107 |