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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
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.
キーワード
ALS
HIF-1 alpha
VEGF
HO-1
EPO
発行日
2012-09-14
出版物タイトル
Brain Research
1473巻
出版者
Elsevier Science Bv
開始ページ
55
終了ページ
62
ISSN
0006-8993
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52529
言語
English
OAI-PMH Set
岡山大学
著作権者
(c) 2012 Elsevier B.V. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT