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Studies on molecular and pathophysiological mechanisms in age related brain disease

Research Project

Project/Area Number 14360189
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

ONO Kenichiro  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (50111480)

Co-Investigator(Kenkyū-buntansha) OGAWA Hiroyuki  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (30012016)
DOI Kunio  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (70155612)
YOSHIKAWA Yasuhiro  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (80109975)
SATO Kota  Tottori University, Faculty of Agriculture, Lecturer, 農学部, 講師 (50283974)
MATSUKI Naoaki  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (40251417)
稲葉 睦  北海道大学, 大学院・獣医学研究科, 教授 (00183179)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥11,400,000 (Direct Cost: ¥11,400,000)
Keywordsage related brain disease / neurological cell death / Ca influx / free radicals / PET / GLAST / glucose metabolism / blood flow / GLUST
Research Abstract

Molecular and pathophysiological mechanisms in age related brain disease were investigated for 2 years (2002-2003) and following results were obtained.
1)Pathophysiolosical mechanisms and free radicals : Free radicals, especially hydroxyradical, were closely related to neurological cell death via Ca influx with a disturbance of voltage-dependent Ca channels in cell membrane. Prine metabolism, such as degradation of high energy phophate components, was remarkably increased and generation of free radicals was developed in neuronal cells during the ischemic condition.
2)Molecular bases analysis for age related brain disease : Registration between PET and MR1 images was carried out and the method of it was established for evaluating the regions of blood flow and/or glucose metabolism. Dementia dogs showed a decrease of blood flow and also glucose metabolism in brain, especially in cortex compared with, those in clinically healthy dogs. In histpathological findings, almost of all animals including wild animals examined showed senile plaque and perivascullar deposits of amiloid protein, like as those in aged man. Those histpathological findings were clearly associated with age advanced. In addition, visual evoked potentials (VEP) were also evaluated. Aged Beagle dogs showed a prolonged latency of P2 (peak 2) with age advanced and VEP was considered to be an available tool for diagnosis of aged brain disease.
3) Animal model of aged brain disease : The recurrent spontaneous epileptic model was made an attempt to rats injected intracranially with iron chloride. All rats injected showed epileptic seizure by 4 months after the treatment. Concentrations of aspartate, glutamate, taurine, and GABA decreased in brain, however pathophysiological effects of those were not completely elucidated.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report

Research Products

(21 results)

All Other

All Publications (21 results)

  • [Publications] Sato, K., et al.: "Cloning and characterization of excitory amino acid transporters GLT-1 and EAAC1 in canine brain."J.Vet.Med.Sci.. 63. 997-1002 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamahara, S. et al.: "Non-essential roles of cysteine residues in functional expression and redox regulatory pathways for canine glutamate/aspartate transporter based on mutagenic analysis."Biochem.J.. 366. 1-5 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, Y. et al.: "Mapping adenosine A1 receptors in the cat brain by positron emission tomography with [11C] MPDX."Nuc.Med.Biol.. 29. 29-37 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamato, O. et al.: "Sandhoff disease in a golden retriever dog."Inherit.Metab.Dis.. 25. 319-320 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nariai, T. et al.: "PET imaging of adenosine A(1) receptors with (11)C-MPDX as an indicator of severe cerebral ischemic insult."J.Nucl.Med.. 44. 1839-1844 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, Y. et al.: "Quantitative in vivo measurement of central benzodiazepine receptors in the brain of cats by use of positron-emission tomography and [11C]flumazenil."Am.J.Vet.Res.. 64. 999-1002 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuki, N. et al.: "Prevalance of autoantibody in cerebrospinal fluids from dogs with various CNS diseases."J.Vet.Med.Sci.. 66. 295-297 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, K., Inaba, M., Baba, K., Tamahara, S., Koshino, I., Hikasa, Y., Ono, K., Kagota, K: "Cloning and characterization of excitory amino acid transporters GLT-l and EAAC 1 in canine brain."J.Vet.Med.Sci.. 63. 997-1002 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tamahara, S., Inaba, M., Sato, K., Matsuki, N., Hikasa, Y., Ono, K.: "Non-essential roles of cysteine residues in functional expression and redox regulatory pathways for canine glutamate/aspartate transporter based on mutagenic analysis"Biochem.J.. 366. 1-5 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, Y., Ishiwata, K., Kiyosawa, M., Nagaoka, T., Oda, K., Toyama, H., Suzuki, F., Ono, K., Senda, M.: "Mapping adenosine Al receptors Mapping adenosine Al receptors in the cat brain by positron emission tomography with [11C]MPDX."Nuc.Med.Sci.. 29. 29-37 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamato, O., Matsuki, N., Satoh, H., Inaba, M., Ono, K., Yaniasaki, M., Maede, Y.: "Sandhoff Disease in a golden retriever dog"J.Inherit.Metab.Dis. 25. 319-320 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nariai, T., Shimada, Y., Ishiwata, K., Nagaoka, T., Shimada, J., Kuroiwa, T., Ono, K., Ohno, K., Hirakawa, K., Senda, M.: "PET imaging of adenosine Al receptors with (11)C-MPDX as an indicator of severe cerebral ischemic insult."J.Nuc.Med.. 44. 1839-1844 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, Y., Kiyosawa, M., Nariai, T., Oda, K., Toyama, H., Ono, K., Senda, M., Ishiwata, K: "Quantitative in vivo measurement of central benzodiazepine receptors in the brain of cats by use of positron-emission tomography and [11C]flumazenil."Am.J.Vet.Res.. 64. 999-1002 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuki, N., Fujiwara, K., Tamahara, S., Uchida, K., Matsunaga, S., Nakayama, H., Doi, K., Ogawa, H., Ono, K.: "Prevalence of autoantibody in cerebrospinal fluids from dogs with various CNS diseases."J.Vet.Med.Sci. 66. 295-297 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nariai, T.et al.: "PET imaging of adenosine A(1) receptors with (11)C-MPDX as an indicator of severe cerebral ischemic insult."J.Nucl.Med.. 44. 1839-1844 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada, Y.et al.: "Quantitative invivo measurement of central benzodiazepine receptors in the brain of cats by use of positron-emission tomography and [11C]flumazenil."Am.J.Vet.Res.. 64. 999-1002 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuki, N. et al.: "Catabolism of cytoplasmic and mitochondria adenosine nucleotides in C2C12 skeletal myotube under chemical hypoxia"J.Vet.Med.Sci.. 64. 341-347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Boffi, F.M.et al.: "Effects of chemical ischemia on purine nucleotides, free radical generation, lipids peroxidation and intracellular calcium levels in C2C12 myotube derived from mouse myocytes"J.Vet.Med.Sci.. 64. 483-488 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamahara, S. et al.: "Non-essential roles of cysteine residues in functional expression and redox regulatory pathways for canine glutamate/aspartate transporter based on mutagenic analysis"Biochem.J.. 366. 1-5 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimada, Y.: "Mapping adenosine A1 receptors in the cat brain by positron emission tomography with [11C]MPDX"Nuc.Med.Biol.. 29. 29-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamato, O.: "Sandhoff disease in a golden retriever dog"J.Inherit.Metab.Dis.. 25. 319-320 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-03-31   Modified: 2016-04-21  

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