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1994 Fiscal Year Final Research Report Summary

Studies on the Machanism of Memory Disturbances in Senescence-Accelerated Mouse and the Application to Screening of Nootropics

Research Project

Project/Area Number 04557120
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionHokkaido University

Principal Investigator

NOMURA Yasuyuki  Hokkaido University, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (00034041)

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)
Project Period (FY) 1992 – 1994
KeywordsAging / Mouse / Memory disturbance / Therapeutics / Herbs / Screening / Pharmacology / Neurochmistry
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.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yoshihisa Kitamura: "Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced dopamine-depletion in the striatum of young C57BL/6 mice" J. Neuroimmunol. 50. 221-224 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki,Hasegawa: "Monoamine content of the brain in the neurofilament-deficient quail,(the quiver quail)" Biol. Pharm. Bull.17(8). 1053-1055 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashi Uehara: "Possible involvement of protein kinase C and low molecular weight GTP-binding proteins in thrombin induced-histamine secretion in human platelets" Biochem. Biophys. Res. Commun. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuyuki Nomura: "Neurochemical studies on aging in SAM brain" The SAM Model of Senescence(T. Takeda ed) Excerpta Medica, Amsterdam/Tokyo,. 83-88 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村靖幸: "脳細胞におけるNO合成酵素-活性,発現の制御と機能" 血管と内皮. 4(6). 614-621 (1994)

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      「研究成果報告書概要(和文)」より
  • [Publications] 野村靖幸: "脳機能の解明, 創風社" 脳の老化-神経細胞死と記憶障害-, 50-57 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村靖幸: "「最新医学からのアプローチ(13)NO」(戸田 昇編)" グリアでのNO産生とニューロン死 (印刷中), (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kitamura, X-H.Zhao, T.Ohnuki, M.Takei, and Y.Nomura: "Age-related changes in transmitter glutamate and NMDA receptor/channels in the brain of senescence-accelerated mouse." Neurosci.Lett.137. 169-172 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] X-H.Zhao, Y.Kitamura, and Y.Nomura: "Age-related changes in NMDA-induced [^3H]acetylcholine release from brain slices of senescence-accelerated mouse." Int.J.Develop.Neurosci.10. 121-129 (1992)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Itano, T.Murayama, Y.Kitamura, and Y.Nomura: "Glutamate inhibits adenylate cyclase activity in dispersed rat hippocampal cells directly via an N-methyl-D-aspartate-like metabotropic receptor." J.Neurochem.59. 822-828 (1992)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Homma, Y.Watanabe, T.Abiru, T.Murayama, Y.Nomura, and A.Matsuda: "Nucleosides and Nucleotides. 112, 2-(1-Hexyn-1-yl) adenosine-5'-uronamides : a new entry of selective A_2 adenosine receptor agonists with potent antihypertensive activity." J.Med.Chem.35. 2881-2890 (1992)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kitamura, A.Miyazaki, T.Yamanaka, and Y.Nomura: "Stimulatory effects of protein kinase C and calmodulin kinase II on NMDA receptor/channels in the postsynaptic density of rat brain." J.Neurochem.61 (1). 100-109 (1993)

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      「研究成果報告書概要(欧文)」より
  • [Publications] M.Tohda, T.Takasu, J.Nakamura, N.Morii, S.Narumiya, and Y.Nomura: "Inhibitory effects of botulinum toxin on 5-HT_<1C> receptor-induced C1 current in Xenopus oocytes." Europ.J.Pharmacol.266. 19-24 (1994)

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      「研究成果報告書概要(欧文)」より
  • [Publications] F.Okada, T.Horikawa, Y.Tokumitsu, and Y.Nomura: "Chronic desipramine treatment influenced D1 stimulation and D2 inhibition (dual control) of adenylate cyclase by dopamine in rat striatum." Neurochem.Int.24 (1). 23-27 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kitamura, Y.Itano, T.Kubo, and Y.Nomura: "Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced dopamine-depletion in the striatum of young C57BL/6 mice." J.Neuroimmunol.50. 221-224 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Hasegawa, T.Murayama, A.Takahashi, C.Itakura, and Y.Nomura: "Monoamine content of the brain in the neurofilament-deficient quail, (the quiver quail)." Biol.Pharm.Bull.17 (8). 1053-1055 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kitamura, T.Arima, T.Sano, J.Nakamura, and Y.Nomura: "Inhibitory effects of pentamidine on N-methyl-D-aspartate (NMDA) receptor/chennels in the rat brain." Biol.Pharm.Bull.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kitamura, T.Arima, R.Imaizumi, T.Sato, and Y.Nomura: "Inhibition by pentamidine on constitutive nitric oxide synthase in the brain : as a calmodulin antagonist." Europ.J.Pharmacol.in press. (1995)

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      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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