| Project/Area Number |
09558098
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Showa University |
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Principal Investigator |
SHIODA Seiji Showa University, Sch. Med., Professor, 医学部, 教授 (80102375)
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| Co-Investigator(Kenkyū-buntansha) |
IWASE Michiko Showa University, Sch. Med., Assistant Professor, 医学部, 講師 (80119164)
MIZUSHIMA Hidekatsu Showa University, Sch. Med., Assistant Professor, 医学部, 講師
NAKAJO Shigeo Showa University, Sch. Pharm., Associate Professor, 薬学部, 助教授 (50119236)
YAGI Takeshi National Inst., Physiol. Sci., Associate Professor, 生理学研究所, 助教授 (10241241)
YADA Toshihiko Kagoshima University, Sch. Med., Associate Professor, 医学部, 助教授 (60166527)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | PACAP / Delayed neuronal cell death / Signal transduction / Transgenic mouse / 免疫組織化学 / 遺伝子組織化学 / マウス / ラット |
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| Research Abstract |
We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of members of the mitogen-activated protein (MAP) kinase family, including extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress. These suggest that PACAP acts to inhibit the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis. We have recently succeeded to make PACAP receptor transgenic mice, therefore we are now trying to clarify direct effect of PACAP on inhibiting neuronal cell death via its specific receptors.
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