| Project/Area Number |
61870107
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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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 | Osaka University |
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Principal Investigator |
YOSHIDA Hitoshi Osaka Uversity, Medical Schoo, 医学部, 教授 (70028273)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHIRO Masanobu Osaka University Medical School, 医学部, 助手 (00172388)
OSUGI Takeshi Osaka University Medical School, 医学部, 助手 (50176880)
WATANABE Tasuhiro Osaka University Medical School, 医学部, 講師 (90127324)
UCHIDA Shuji Osaka University Medical School, 医学部, 助教授 (90028639)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1987: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1986: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | quinolinic acid / PrBCM (propylbensilylcholine mustard) / memory / PrBCM(propylbenzilyl chaline mustard) / ムスカリニックアセチルコリン受容体 |
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| Research Abstract |
Our project is to make animal models having deficency in learning and memory, especially in relation with Alzheimer's desease. In Alzheimer's patients it is generally known that there is degenration in Meynert nucleus which contains chelinergic neurons innervationg the frontal and parietal cortices. Standing on these considetations we carried experimaents and following resuls were obtained.
I) Injection of prBMC (proplybenzilylcholine mustard), irrversible antagonist of muscatinic acetylcholine receptor, into rat brain frontal and parietal cortices caused dificit in passive avoidance learning. But its injection into the occipital cortex did not cause significant deficit. Furthermore we examine the effect of prBCM on three phases of the memory, acquisition, retention and recalling phase. By out results, acquisition and recalling phases were impaired by prBCM byt retention phase was not significantly influenced by the injection.
II) In shuttle active aboicdance leatning we also observed a deficient by injection of PrBCM iinto fronatl and parieral cortices of the rat. These results indicate that impairment in cholinergin synapses caused deficits in leatning and memory process.
III) In search for endfogenous substances which cause degeneration of cholinergic neurons, we found taht injection of quinolinic acid, a metablit tryptophan, into basal nucleus to Meynert caused degenetation of cholinergic neuron in rat brain cortex by estimation of CAT (choline acetyl transterase) activity. Behavioral study on learning- and memory on these quinolinatetrasted rats progressed in our laboratory new. In the other hand we found that quainolinic acid have high affinity on gultamate receprots by binding experiments with^3H-gultamate of^3H-CPP (3-(2-carboxypiperazin-4yl)-propyl-phosphoric acid). This quinolinic acid-trated rats maybe one type of deficit model animal on learning and memory.
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