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Development of model animals and cells for neuronal disease

Research Project

Project/Area Number 09357019
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

NOMURA Yasuyuki  Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (00034041)

Co-Investigator(Kenkyū-buntansha) SHUTO Satoshi  Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (70241346)
MURAYAMA Toshihiko  Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (90174317)
OKUMA Yasunobu  Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助教授 (20127939)
HATTORI Masao  Research Institute for Oriental Med., Toyama Medical & Pharmaceutical Univ., Prof., 和漢薬研究所, 教授 (40126545)
UEHARA Takashi  Grad. School of Pharm. Sci., Hokkaido University, Associate Prof., 大学院・薬学研究科, 助手 (00261321)
松田 彰  北海道大学, 大学院薬学研究科, 教授 (90157313)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥35,300,000 (Direct Cost: ¥35,300,000)
Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1997: ¥19,000,000 (Direct Cost: ¥19,000,000)
Keywordssenescence accelerated mouse / learning impairments / depressive behavior / ischemia / neuronal death / GDNF / aging / 加齢 / senescence accelerated mouse(SAM) / differential display法 / グルタミンシンテターゼ / 促進老化マウス / 虚血モデル / 神経伝達物質 / 受容体 / ストレス刺激 / アポートシス / NO
Research Abstract

The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previously, we reported that SAMP8 and SAMP10 exhibit age-related learning impairments . In this study, we investigated the changes in emotional behavior and in neurotansmitter receptor in SAMP10, and the effect of onion extract on learning ability in Morris's water maze test.
1) SAMP10 at 8 months showed an increases of immobility in a forced swimming test compared with SAMR1. Treatment with desipramine (25 mg/kg, I.p., 3 days) in SAMP10 caused a decrease in immobility.
2) In the cortex from SAMP1O, [ィイD13ィエD1H]quinpirol binding to D2/D3 dopamine receptors increased significantly. In the hippocampus from SAMP10, [ィイD13ィエD1H]hydroxy DPAT binding to 5-HTィイD11AィエD1 receptors increased.
3) In Morris's water maze task, in a control strain of SAMR1 at 8 months, the escape latency and path length decreased with increasing trial days, in contrast, the escape latency and path length did not change in SAMP8. Treatment with onion extract (5 ml/kg, p.o., 2 months) in SAMP8 improved the learning and memory in the task.
4) In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA 1 region was observed 7 days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1 μg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the neuronal death. CV-159 (a dihydropyridine derivative) that blocks the L-type CaィイD12+ィエD1 channel and inhibits the calmodulin-dependent pathway. CV-159 gave protection against delayed neuronal death in the CA1 region after 15-min transient forebrain ischemia.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Nomura Y.et al.: "Alterations in acetylcholine, NMDA, benzodiazepine receptors and protein kinase C in the brain of the senescence-accelerated mouse : an animal model useful for studies on cognitive enhancers"Behav.Brain.Res.. 83. 51-55 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arima T.et al.: "Ameliorating effects of calcium/magnesium lithospermate B on cognitive deficiencies in senescence-accelerated mouse"Kor.J.Gerontol. 7(1). 17-24 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uehara T.et al.: "Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells"Brain Res.. 790. 284-292 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata Y.et al.: "D-serine content and D-[^3H]serine binding in the brain regions of the senescence-accelerated mouse"Mech.of Ageing Develop.. 104. 115-124 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki H.et al.: "Neuroprotective effects of a dihydropyridine derivative, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-pheneyl-3-pyrazolyloxy) hexyl ester (CV-159), on rat ischemic brain injury"Life Sci.. 64(10). 869-878 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka S.et al.: "Upregulation of protein disulfide isomerase in response to hypoxia/brain is chemia and its protective effect against apoptotic cell death"J.Biol.Chem.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura Y.et al.: "Research and Practice in Alzheimer's Disease"Serdi Publisher (Paris). 5 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura Y.et al.: "Innovative Animal Models of Central Nervous System Disease"The Humana Press (Massachusetts). 9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura, Y. et al: "Alterations in acetylcholine, NMDA, beniodiazepine receptors and protein kinase C in the brain of the senescence-accelerated mouse : an animal model useful for studies on cognitive enhancers."Behav. Brain. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Arima, T. et al: "Ameliorating effects of calcium/magnesium lithospermate B on cognitive deficiencies in senescence-accelerated mouse."Kor. J. Gerontol..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uehara, T. et al: "Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells."Brain Res..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata, Y. et al: "D-serine content and D-[ィイD13ィエD1H]serine binding_in the brain regions of the senescence-accelerated mouse"Mech. Of Ageing Develop..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki, H. et al: "Neuroprotective effects of a dihydropyridine derivative, 1,4-dibydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyidinedicarboxylie acid methyl 6-(5-pheneyl-3-pyrazolyloxy)hexyl ester(CV-159),on rat ischemic brain injury"Life Sci..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka, S. et al: "Upregulation of protein disulfide isomerase in response to hypoxia/brain is chemia and its protective effect against apoptotic cell death."J. Bial. Chem..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura, Y. et al: "Senescence-accelerated mouse (SAM) as an animal model of senile dementia : Neurochemical and pharmacological studies."Reseach and Practice in Alzheimer's Disease.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura, Y. et al: "The senescence accelerated mouse (SAM) as a possible animal model of senile dementia Innovative Animal Models of Central."Nervous System Disease.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki, H. et al.: "Neuroprotective effects of a dihydropyridine derivative, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester(CV-159), on rat ischemic brain injury"Life Sci.. 64(10). 869-878 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uehara, T. et al.: "Caspase activation accompanying cytochrome C release from mitochondria is possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells"J. Neurochem.. 72(1). 196-205 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uehara, T. et al.: "Possible involvement of p38 MAP kinase in HSP70 expression induced by hypoxia in rat primary astrocytes"Brain Res.. 823. 226-230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uehara, T. et al.: "Transient NF-κB activation stimulated by interleukin-1β may be party dependent on proteasome activity, but not phosphorylation and ublquitination of IκBα molecule, in C6 glioma cells"J. Biol. Chem.. 274(22). 15875-15882 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito, A. et al.: "Possible involvement of cytochrome c release and sequential activation of caspases in ceramide-induced apoptosis in SK-N-MC cells"Biochem. Biophys. Acta. 1452. 263-274 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka, S. et al.: "Upregulation of protein disulfide isomerase in response to hypoxia/brain is chemia and its protective effect against apoptotic cell death"J. Biol. Chem.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nomura, Y. et al: "Research and Practice in Alzheimer's Disease"Serdi Publisher (Paris). 5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nomura, Y. et al: "Innovative Animal Models of Central Nervous System Disease"The Humana Press (Massachusetts). 9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagata,Y.et al: "D-serine content and D-[^3H] serine binding in the brain regions of the senescence-accelerated mouse." Mech.of Ageing Dev.104. 115-124 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Araya,R.et al: "Hypoxia induces apoptosis human neuroblastoma SK-N-MC cells by caspase activation accompanying cytochrome C release from mitochondria." FEBS Lett.439. 168-172 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uehara,T.et al: "Caspase activation accompanying cytochrome C release from mitochondria is possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells." J.Neurochem.72・1. 196-205 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maekawa,M.et al: "Stimulation of noradrenaline release by T-588,a cognitive enhancer,in PC12 cells." Biochem.Pharmacol.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyazaki,H.et al: "Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats." Neuroscience. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Maekawa,M.et al: "Effects of T-588,a novel cognitive enhancer,on ADP-ribosylation of Gsα by cholera toxin and cyclic AMP accumulation in rat cerebral cortex." Neurochem.Int.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,Y.et al: "The senescence accelerated mouse (SAM) as a possible animal model of senile dementia. in “Innovative Animal Models of Central Nervous System Disease"" The Humana Press,Inc.,Mass.USA. (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,Y.et al: "Senescence-accelerated mouse (SAM) as an animal model of senile dementia : Neurochemical and pharmacological studies." Service de Medecine Interne et Gerontologie Clinique,Toulouse,France (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,Y., et al: "Alteralions in acelylclroline,NMDA,benzodiazepine receplors and prolcin kinase C in the bral of the senescence-accelerated mousc:an animal model useful for studies on cognitive enhancers." Behav.Brain.Res.83. 51-55 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kamoshima,W., et al: "Possible involvement of ADP-ribosylation of particular enzymes in cell death induced by nitric oxide-donors in human neuroblastoma." Neurochem.Int.30・3. 305-311 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kitamura,T., et al: "Inhibitory effecls of talipexole on MPTP-induced dopamine reduction in the strialum of C57BL/6N mice." Japan.J.pharmacol.74. 51-57 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakazawa,M., et al: "Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase (GAPDH)inhibitor)induced-fragmentation and-condensation of DNA in NG lO8-15 cells." J. Neurochem.68・6. 2493-2499 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oda,H., et al: "Inhibition of inducible nitric oxide synthase expression by endothelin inrat glial cells prepared from the neonatal rat brain." J.Neurochem.69・2. 669-674 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arima,T., et al: "Ameliorating effects of calcium/magnecium lithospermate B on cognitive deficiencies in senescence-accelerated mouse." Kor.J.Gerontol.7・1. 17-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 野村靖幸: "脳虚血への血管系・グリア・ニューロン応答と薬物作用" 日本薬理学雑誌, 3 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 野村靖幸: "アストロサイトにおけるNO合成酵素の誘導と脳ニューロン死,「脳機能の解明」(赤池紀扶編)" 九州大学出版会(印刷中), (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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