| Project/Area Number |
07557009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General pharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
NABESHIMA Toshitaka Nagoya University School of Medicine, Department of Neuropsychopharmacology and Hospital Pharmacy, Professor, 医学部, 教授 (70076751)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Ken-ichi Mitsubishi Chemical Corporation, Yokohama Research Center, Senior Research Scien, 主任研究員
HASEGAWA Takaaki Nagoya University School of Medicine, Department of Neuropsychopharmacology and, 医学部, 助教授 (80198720)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Alzheimer's disease / beta-amyloid protein / learning and memory / animal models / acetylcholine / neuronal transmission / therapeutics / アルツハイマー型老年期痴呆 / 学習記憶 / プロペントフィリン / メトリフォネイト / アセチルコリンエステラーゼ阻害剤 / 神経成長因子 / 一酸化窒素 / アルツハイマー型痴呆症 / in vivo brain dialysis法 / ニコチン / ドパミン / 毛様体神経栄養因子 |
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| Research Abstract |
We have investigated to develop animal models for Alzheimer's disease (AD) by continuous infusion of beta-amyloid protein (Abeta) into the cerebral ventricle of rats. The results obtained during the aid are as follows :
In rats continuously infused Abeta,
1 impairments of learning and memory were observed.
2 deposition, of Abeta and decrease of choline acetyltransferase activity were observed in the cerebral cortex and hippocampus which play key roles in learning and memory.
3 expression of glial fibrillary acidic protein, an index of gliosis, was increased in the hippocampus.
4 ciliary neurotrophic factor content was increased in the cerebral cortex and hippocampus.
5 nicotine- or high-K-evoked release of acetylcholine and dopamine in the cortex/hippocampus and striatum, respectively, was decreased.
6 less electrophysiologicalresponse against nicotine in the hippocampal CAl pyramidal cells was observed.
7 disability on induction of long-term potentiation in the hippocampal CAl pyramidal cells was observed.
8 decrease of nicotine-induced enhancement of paired-pulse facilitation in the hippocampal CAl pyramidal cells was observed.
9 administration of cognitive enhancers such as nefiracetam, propentofylline, arginine-vasopressin derivatives, idebenone and alpha-tocopherol, improves impairments of learning and memory induced by Abeta infusion.
These results suggest that continuous infusion of Abeta is a good method to prepare the animal model of AD,which exhibits similar features observed in human AD patients. Moreover, this model is useful to evaluate the novel compounds for treatment of AD.
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