| Project/Area Number |
08457634
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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 | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
WATANABE Hiroshi Toyama Medical and Pharmaceutical University Inst for Natural Med., Dept.of Pharmacol.Professor, 和漢薬研究所, 教授 (10012642)
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| Co-Investigator(Kenkyū-buntansha) |
TOHDA Michihisa Toyama Medical and Pharmaceutical University Inst for Natural Med., Dept.of Phar, 和漢薬研究所, 助手 (20207525)
MATUSMOTO Kinzo Toyama Medical and Pharmaceutical University Inst for Natural Med., Dept.of Phar, 和漢薬研究所, 助教授 (10114654)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | learnig and memory / common carotid artery / infarction / radial maze / gene expression / chronic cerebral hypoperfusion / rat brain / 両側総頚動脈永久結紮 / 空間学習行動 / 免疫組織化学 / タクリン / 遺伝子発現 / ニコチン性受容体アゴニスト / 脳血管性障害 / 痴呆モデル動物 / differential display / in situ hybridization |
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| Research Abstract |
A variety of animal models have been used to investigate the behavioral and pathophysiological changes observed in human dementia, and to pharmacologically elucidate activities of putative anti-amnesiac drugs. Although it is generally accepted that progressive cognitive dySfunction occurs in human dementia, cognitive deficits observed in these animal models are usually transient and recover to a normal level in a time-dependent manner. In this study, we investigated the influences of permanent occlusion of bilateral common carotid arteries (2VO) in rat on learning and memory performance, histological changes in brain and gene expression changes to evaluate the 2VO rats as a model for vascular dementia.
1) The results from the 8-arm radial maze task show that 2VO disrupted both working and reference memory. Tacrine, a cholinesterace inhibitor, improved the working memory deficit.
2) 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in cerebral cortex and hippocampus at early stage after 2VO.These histological changes were accompanied by a decrease in immunoreactivity for MAP-2 and increase in GFAP immunoreactivity. Shimotsu-to, a Kanpo medicine, and GST-21, a nicotinic acetylcholine receptor agonist1 had protective effects on these histological damage induced by 2VO.
3) Some kind of genes which changed the expression by 2VO were isolated. The expression enhancement of a novel factor named vof-16 (Accession No. AB006881) had a correlation with memory deficit detected by 8-arm radial maze task.
Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.
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