| Project/Area Number |
16591448
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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 | Kumamoto University |
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Principal Investigator |
YANO Shigetoshi Kumamoto University, Neurosurgery, Instructor, 医学部附属病院, 助手 (60332871)
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| Co-Investigator(Kenkyū-buntansha) |
MORIOKA Motohiro Kumamoto Univ., Neurosurgery, Assistant Professor, 医学部附属病院, 講師 (20295140)
KAI Yutaka Kumamoto University, Neurosurgery, Instructor, 大学院・医学薬学研究部, 助手 (30322308)
MORI Masataka Kumamoto University, Morecular Genetics, Professor, 大学院・医学薬学研究部, 教授 (40009650)
濱田 潤一郎 熊本大学, 医学部附属病院, 講師 (40253752)
河内 正人 熊本大学, 大学院・医学薬学研究部, 助教授 (70178218)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | CHOP / ER stress / BiP / hypoxia / ischemia / apoptosis / BiP / アポトーシス / 海馬 / 線条体 / 脳虚血 / Bip |
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| Research Abstract |
To investigate the roll of ER stress on neuronal cell death in cerebral ischemia, we focused on CHOP which is inducible ER-stress protein and known to induce apoptosis.
When wild-type mice were subjected to bilateral common carotid arteries occlusion (BCCAO) for 15 min, apoptosis-associated morphological changes and appearance of TUNEL-positive cells were observed in the striatum and in the hippocampus at 48 h after occlusion. RT-PCR analysis revealed that mRNAs for ER stress-associated proapoptotic factor CHOP and an ER chaperone BiP are markedly induced at 12 h after BCCAO. Immunohistochemical analysis showed that CHOP protein is induced in nuclei of damaged neurons at 24 h after occlusion. In contrast, ischemia-associated apoptotic loss of neurons was decreased in CHOP(-/-) mice. Primary hippocampal neurons from CHOP(-/-) mice were more resistant to hypoxia-reoxygenation-induced apoptosis than those from wild-type animals. These results indicate that ischemia-induced neuronal cell death is mediated by the ER stress pathway involving CHOP induction.
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