ID | 52805 |
フルテキストURL | |
著者 |
Sato, Kota
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Morimoto, Nobutoshi
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Kurata, Tomoko
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Mimoto, Takafumi
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Miyazaki, Kazunori
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Ikeda, Yoshio
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Abe, Koji
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol
Kaken ID
publons
researchmap
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抄録 | We have recently reported spinal blood flow-metabolism uncoupling in an amyotrophic lateral sclerosis (ALS) animal model using Cu/Zn-superoxide dismutase 1 (SOD1)-transgenic (Tg) mice, suggesting a relative hypoxia in the spinal cord. However, the hypoxic stress sensor pathway has not been well studied in ALS. Here, we examined temporal and spatial changes of the hypoxic stress sensor proteins HIF-1 alpha and its downstream proteins (VEGF, HO-1, and EPO) during the normcodccourse of motor neuron (MN) degeneration in the spinal cord of these ALS model mice. We found that HIP-1 alpha protein expression progressively increased both in the anterior large MNs and the surrounding glial cells in Tg mice from early symptomatic 14 week (W) and end stage 18W. Double immunofluorescence analysis revealed that HIP-1 alpha, plus GFAP and Iba-1 double-positive surrounding glial cells, progressively increased from 14 W to 18 W, although the immunohistochemistiy in large MNs did not change. Expression levels of VEGF and HO-1 also showed a progressive increase but were significant only in the surrounding glial cells at 18W. In contrast, EPO protein expression was decreased in the surrounding glial cells of Tg mice at 18W. Because HIF1-alpha serves as an important mediator of the hypoxic response, these findings indicate that MNs lack the neuroprotective response to hypoxic stress through the HIF-1 alpha system, which could be an important mechanism of neurodegeneration in ALS.
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キーワード | ALS
HIF-1 alpha
VEGF
HO-1
EPO
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発行日 | 2012-09-14
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出版物タイトル |
Brain Research
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巻 | 1473巻
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出版者 | Elsevier Science Bv
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開始ページ | 55
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終了ページ | 62
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ISSN | 0006-8993
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資料タイプ |
学術雑誌論文
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52529
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言語 |
英語
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著作権者 | (c) 2012 Elsevier B.V. All rights reserved.
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |