| Project/Area Number |
04557120
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| Research Category |
Grant-in-Aid for Developmental 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 | Hokkaido University |
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Principal Investigator |
NOMURA Yasuyuki Hokkaido University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (00034041)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Yoshihisa Toyama Medical and Pharmaceutical University Associate Professor, 助教授 (60195295)
OKADA Fumihiko Hokkaido University, Health Center Associate Professor, 保健管理センター, 助教授 (40109517)
TOKUMITSU Yukiko Hokkaido University, Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (60001046)
MATSUDA Akira Hokkaido University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (90157313)
KIKUCHI Tohru Toyama Medical and Pharmaceutical University Professor, 和漢薬研究所, 教授 (40025680)
東田 道久 北海道大学, 薬学部, 教務職員 (20207525)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥17,900,000 (Direct Cost: ¥17,900,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1993: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1992: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | Aging / Mouse / Memory disturbance / Therapeutics / Herbs / Screening / Pharmacology / Neurochmistry / 脳内機序 / 神経伝達物質受容体 / 薬効評価法 / 脳機能障害 / 老化促進マウス / 海馬 / M_1ムスカリン受容体 / NMDA型グルタミン酸受容体 / GABA受容体 / プロテインキナーゼC |
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| Research Abstract |
Senescence-accelerated mouse (SAM) has been esstablihed as a murine model showing accelerating aging. Memory impairment with aging is also observed in P8 strain (SAMP8) in contrast to the control (SAMR1). To establish the methodology screening effective drugs with anti-aging and memory improvement, we investigated effects of herbs on memory disturbance using SAMP8. The methanol extract from Tan-jin, an oriental medicine with improving effects on peripheral microcirculation disturbances at 500 mg/kg/day was orally administrated five time a week for 3 weeks into 4-month-old mice. Spatial recognition ability was evaluated by the Morris water maze methods. The extract ameliorated spatial recognition compared to the vehicle control. In addition, the extract did not affect locomotor activity but shortened the immobility time in the water bath. Therefore the methanol extract from Tan-jin contains active chemicals improving the brain functions. We then measured [^3H]MK-801 binding (to NMDA receptors) and [^3H]N^G-nitro-arginine ([^3H]NNA) binding (to nitric oxide synthase) in regional brains of SAMP8 treated with the extract. The treatment increased the [^3H]MK-801 binding in cerebral cortex and [^3H]NNA binding in brain stem, suggesting that Tan-jin is effective on synaptic neurotransmission and neurotransmittor receptor-mediated transmembrane signaling in the brain. We still are investigating following points : 1) identification of active chemicals, 2) the cellular and moleular mechanism of the action, 3) clinical application to patients with mental and intellectual disturbances. We can propose that SAMP8 is an useful animal model studying the mechanism of age-related memory impairment and screening the therapeutic drugs.
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