| Project/Area Number |
05670572
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
TANAKA Kotaro DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,ASSISTANT PROFESSOR, 医学部, 専任講師 (90129528)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Eiichiro DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (00255457)
NOZAKI Hiroyuki DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (80218312)
NOGAWA Shigeru DEPARTMENT OF NEUROLOGY,SCHOOL OF MEDICINE,KEIO UNIVERSITY,INSTRUCTOR, 医学部, 助手 (50208310)
近藤 太郎 慶應義塾大学, 医学部, 助手 (40234942)
白井 俊孝 慶應義塾大学, 医学部, 助手 (80196592)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | AMYOTROPHIC LATERAL SCLEROSIS / DEMENTIA / INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR / HIPPOCAMPUS / RYANODINE RECEPTOR / イノシトール1,4,5三リン酸受容体 |
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| Research Abstract |
We have investigated the role of type 1 inositol 14,5-trisphosphate receptor (IP3R1) in the morphogenesis of the central nervous system and the behavioral development. In mice lacking IP3R1 generated by gene targeting, microscopic examination revealed no abnormality in the histological sections of each structure fo the brain, which were stained by hematoxyline-eosin or anti-microtubule-associated protein 2. Western blot analysis showed that homozygote (IR3R1 -/-) has no IP3R1 protein, but normal amounts of IP3R2 and IP3R3. IP3 binding was significantly reduced all over the brain in the homozygote mice. At postnatal day (PND) of 9, homozygote began to show ataxia. At PND 15, truncal trosion appeared, and repetitive tonic or tonic-clonic seizures prevailed by PND 20-23. Electroencephalogram showed a paroxysmal polyspike activites. Such generalized seizures were suppressed by intraperitoneal injection of pentobarbital or diazepam. Taken together, IP3R1 seems to play an important role in the regulation of not only cerebellar function but also of the excitability of the neural networks.
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