| Project/Area Number |
11670155
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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 |
Pathological medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
SATOH Takumi Osaka Bioscience institution, Department of Neuroscience, Research Associate, 第3研究部, 研究員 (10300831)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Masaaki Department of Biomolecular Science, Faculty of Engineering, Gifu University, Professor, 工学部・生命工学, 教授 (90093046)
WATANABE Yasuyoshi Department of Physiology, Osaka City University, Graduate School of Medicine, Professor, 医学部・生理学, 教授 (40144399)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Prostacyclin / Prostaglandin / 15R-TIC / Apoptosis / Neuronal death / Hippocampus / Septum |
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| Research Abstract |
Prostacyclin (PGI2) is a critical regulator of the cardiovascular system. Our previous studies demonstrated that a novel subtype of PGI2 receptor, which is clearly distinct from a peripheral subtype in terms of ligand specificity, is expressed in the rostral region of the brain. CNS-specific PGI2 receptor ligands prevented the neuronal death. They prevented apoptotic cell death of hippocampal neurons induced oxidative stress. The effective concentrations well correlated with the binding potency for the CNS-specific PGI2 receptor. They also promoted neuronal survival of septal cholinergic neurons in culture. In vivo, 15R-TIC protected CA1 pyramidal neurons against ischemic damage in gerbils and prevented neuronal injury induced by focal ischemia in mice. During the PET study, we found that peripherally-injedted 15R-TIC accumulated in the in the rostral region of the brain. These results indicate that CNS-specific PGI2 ligands have neuronal survival-promoting activity both in vitro and in vivo, and may represent a new type of therapeutic drug for neurodegeneration.
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