| Project/Area Number |
63480477
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Dept. of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University |
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Principal Investigator |
UEKI Showa Kyushu Univ. Pharmacology Prof., 薬学部, 教授 (80037564)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Shigenobu Kyushu Univ. Pharmacology Assist., 薬学部, 助手 (10162629)
YAMAMOTO Tsuneyuki Kyushu Univ. Pharmacology Assist., 薬学部, 助手 (20091332)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Dementia / Impairment of memory / Scopolamine / Cerebral ischemia / Brain slice / ^<14>C-2-deoxyglucose uptake / Nootropic drug / Brain lesion / 記憶・学習 / 抗痴呆薬(向知能薬) / サーカディアンリズム / 回転かご運動 |
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| Research Abstract |
It was attempted to establish dementia models useful for evaluating the effect of nootropic drugs in rats.
1.Working memory of the rat assessed in a 3-panel runway apparatus, using a repeated acquisition procedure, was significantly impaired by an administration of scopolamine or AF64A, lesioning of the hippocampus or olfactory bulb and cerebral ischemia. The impairment of working memory induced by either scopolamine or hippocampal lesions was significantly ameliorated by physostigmine and many nootropic drugs possessing central cholinergic activity, such as minaprine, amiridin, tetrahydroaminoacridine, WEB1881 and so on, but. not by S-adenosyl-L-methionine(SAM). In contrast, the memory impairment induced by cerebral ischemia was ameliorated not merely by these nootropic drugs but also by SAM.
2.The delayed matching to lever location task of rats in a 3-level aperant apparatus was markedly impaired by olfactory bulbectomy and this impairment was reversed by physostigmine.
3.As an in vitro model of cerebral ischemia, rat hippocampus and cortex slices (450mum thick) were incubated for 20 minutes in a hypoxia + hypoglycemia solution and washed out for the next 6 hours. and then 3OmM KCI-induced ^<14>C-2-deoxyglucose(2-DG) uptake of the tissue was measured for a period of 45 minutes. The 2-DG uptake of these slices decreased after being subjected to hypoxia + hypoglycemia for 20 minutes. This decrease in the cerebral glucose utilization was effectively protected by the treatments reducing the adenylate cyclase activity, inositol hosphate turnover or the influx of Ca ion into the cell.
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