Molecular Mechanism of slowly progressive neuronal degeneration after brief ischemia
| Project/Area Number |
14571315
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
DESAKI Junzo Ehime University, School of Medicine, Lecturer, 医学部, 講師 (00036451)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUDA Nonaki Ehime University, School of Medicine, Associate Professor, 医学部, 助教授 (10314329)
RYUJI Hata Ehime University, School of Medicine, Associate Professor, 医学部, 助教授 (90258153)
久門 良明 愛媛大学, 医学部, 助教授 (80127894)
阪中 雅広 愛媛大学, 医学部, 教授 (60170601)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Neuronal cell death / Apoptosis / Cerebral ischemia / Bcl-XL / Stat / 神経細胞死 / Bcl-xL / サイトカイン / 神経細胞長期変性 / 海馬 / スナネズミ / ジンセノサイドRb_1 / 静脈内投与 / 受動的回避学習実験 |
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| Research Abstract |
Slowly progressive degeneration of the hippocampal CA1 neurons was induced by a three-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident in one month after ischemia. To investigate the effects of an 18-mer-peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained, neuronal degeneration, an intracerebroventricular 18MP infusion was initiated three days after ischemia. Histopathological and behavioral evaluations were conducted one week and one month after induction of ischemia. When compared to the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident as was the number of intact synapses in the hippocampal CA1 region at one week. and one month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons one week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1-100 fg/ml prevented nitric oxide (NO)-induced neuronal damage as expected and significantly upregulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of ischemia of a 3-minute duration is useful in studying the pathogenesis of slowly progressive neuronal degeneration following stroke and for evaluating effects of novel therapeutic. agents. It is likely that the 18MP at the low extracellular concentrations prevents neuronal apoptosis possibly through upregulation of the mitochondrial anti-apoptotic factor Bcl-xL.
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain.2002
Author(s)
Heese K, Nakayama T, Hata R, Masumura M, Akatsu H, Li F, Nagai Y, Yamamoto T, Kosaka K, Suemoto T, Sawada T
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Journal Title
Eur J Neurosci 15
Pages: 79-86
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Characterizing CGI-94(comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain.2002
Author(s)
Heese K, Nakayama T, Hata R, Masumura M, Akatsu H, Li F, Nagai Y, Yamamoto T, Kosaka K, Suemoto T, Sawada T.
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Journal Title
Eur J Neurosci 15
Pages: 79-86
Description
「研究成果報告書概要(欧文)」より
Related Report
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