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Development of the animal model for Alzhcimer disease

Research Project

Project/Area Number 06454331
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionOsaka University

Principal Investigator

TAKEDA Masatoshi (1995)  Osaka University, Assistant Professor, 医学部, 講師 (00179649)

西村 健 (1994)  大阪大学, 医学部, 教授 (70028455)

Co-Investigator(Kenkyū-buntansha) KUDA Takashi  Osaka University, Assistant, 医学部, 助手 (10273632)
TANIGUCHI Norio  Osaka University, Assistant, 医学部, 助手 (30263255)
武田 雅俊  大阪大学, 医学部, 講師 (00179649)
播口 之朗  大阪大学, 医学部, 助教授 (10028459)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsAlzheimer disease / animal model / buffy coat / head trauma / aluminum / neurofilament / ニューロフィラメント / バッフィーコート / リン酸化
Research Abstract

The animal models for Alzheimer disease (AD) based on epidemiological factor, metal intoxication, infection, head trauma, were developed and their significance were investigated.
As for infectious factor, we inoculated buffy coat from patients to hamster brains. In the brain injected with buffy coat from AD,accumulations of the fibers immunopositive with anti-phosphorylated neurofilament H (NFH) and anti-tau antibodies were observed in nuclei of brain stem. The third passage experiment, i.e.the inoculatoin of the homogenate from the suffered hamster brain, showed that dephosphorylated NFH was also accumulated.
As a model for head trauma, we beat rats on the heads by fluid percussion. The repetition of mild impact, which effects little damage if single blow, cause high immunoreactivities with anti-MAP2 and anti-pNFH in some neuronal cells. In the impact site, there was neuronal loss with the accumulation of glial fibrillary acidic protein. One month later, even contralateral site showed neuronal loss with the accumulation of p-NFH.
We made aluminum intoxication in rabbit brain as a model of metal intoxication. Time-dependent dissociation between NFH and NFL level was observed in especially intoxicated brain stems. Besides the distribution of these proteins was uneven in altered neurons. The level of mRNA of NFH increased in time-dependent manner in brain stem, but only this phenomenon could not account for the increase of NFH protein. In the process of the NFH accumulations, dephosphorylated forms gathered in early stage, but phosphorylated forms increased gradually instead of dephosporylated NFH.
It is interesting that fibrous accumulations were observed in the brains of three different model. It is suggested that impairment of axonal transport is most common event through the three models.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] 武田雅俊,他: "細胞骨格蛋白からみたアルツハイマー病のモデル動物 -バッフィコート接種実験とリン酸の異常-" 薬物神経行動. 13(6). 407 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 金山 巌,他: "軽微な頭部衝撃の繰り返しにより惹起される細胞骨格蛋白の変化" 神経化学. 33. 220-221 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 西村 健,他: "アルツハイマー病モデル動物の開発" 長寿科学痴呆関係班平成5年度研究業績集. 405-412 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 金山 巌,他: "軽微な頭部頻回衝撃によるタウ蛋白の変化 -Alzheimer病の病理過程との関連性-" 神経化学. 34. 58-59 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田雅俊,他: "頭部外傷の動物モデル" 老年精神医学雑誌. 6(7). 851-864 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 関山敦生: "アルミニウム中毒ウサギ脳におけるニューロフィラメント蛋白動態の経時的変化" 老年精神医学雑誌. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 金山 巌,他: "軽微な頭部頻回衝撃によるタウ蛋白の変化" 神経化学. 34(2). 46-47 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 関山敦生: "アルミニウム中毒ウサギ脳におけるニューロフィラメント蛋白動態の経時的変化" 老年精神医学雑誌. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M. Takeda,et al.: "RESEARCH ADVANCES IN ALZHEIMER'S DISEASE AND RELATED DISORDERS" Johnn Wiley & Sons,New York, 798 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 武田雅俊: "生物学的精神医学6「痴呆の生物学」" 学会出版センター, 189 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Takeda et al: "Animal model of Alzheimer disease based on cytoskeletal pathology-abnormal phosphorylation caused by buffy coat inoculation" Yakubutsu-Seisin-Koudou. 13 (6). 407 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G.Kanayama et al: "Alteration of cytoskeletal proteins caused by repetition of mild impact to the head" Shinkeikagaku. 33. 220-221 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nishimura et al: "Development of animal model for Alzheimer disease" Choujukagaku Gyousekisyu. 405-412 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] G.Kanayama et al: "Alteration of tau protein caused by repetition of mild impact to the head" Shinkeikagaku. 34. 58-59 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Takeda et al: "The animal model of head injury" Rounenseishinigaku. 6 (7). 851-864 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Sekiyama: "Changes of synthesis, localization, and phosphorylation of neurofilament subunits in aluminum intoxicated rabbit brain" Rounenseishinigaku. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Takeda et al: "Neurofilament pathology of Alzheimer's disease : Neurofilament accumulation by Alzheimer buffy coat" Research Advances in Alzheimer's Disease and Related Disorders (K.Iqbal, J.Mortimer, B.Winblad, and H.Wisniewski edd.). 553-559 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Takeda: "Abnormality of cytoskeletal proteins in Alzheimer disease" Seibutsugakutei-Seishinigaku 6 (Japanese Society of Biological Psychiatry ed.). 81-104 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 西村 健 他: "アルツハイマー病動物モデルの開発" 長寿科学痴呆関係班平成5年度研究業績集. 405-412 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 金山 厳 他: "軽微な頭部頻回衝撃によるタウ蛋白の変化" 神経化学. 34(2). 46-47 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田雅俊 他: "頭部外傷の動物モデル" 老年精神医学雑誌. 6(7). 851-864 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 関山 敦生: "アルミニウム中毒ウサギ脳におけるニューロフィラメント蛋白動態の経時的変化" 老年精神医学雑誌. 発表予定.

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Niigawa,et al: "Effects of SDZ ENA713,novel acetylcholinesterase inhibitor,on learning of rats with basal forebrain lesion." Prog Neuro-Psychopharmacol & Psychiat. 19. 171-186 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Tatebayashi,et al: "Cell-cycle-dependent abnormal calcium response in fibroblasts from patients with familial Alzheimer's disease." Dementia. 6. 9-16 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Takeda,et al: "RESEARCH ADVANCES IN ALZHEIMER'S DISEASE AND RELATED DISORDERS" Johnn Wiley & Sons, 798 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田雅俊: "生物学的精神医学6「痴呆の生物学」" 学会出版センター, 189 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Tanimukai et al: "Buffy Coat from Sporadic and Familial Alzheimer's Disease Patients Induces Abnovmal Neurofilament Accumulation in Hamster Brain" Neurobiol.Aging. 15. 34- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Takeda et al Neurofilament Pathology in Alzheimer's disease: Neurobiol.Aging. 15. 139- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田雅俊ほか: "アルツハイマー病患者のバッフィコート接種により生じるハムスター脳内ニューロフィラメントの異常増生" 薬物精神行動. (印刷中). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田雅俊ほか: "細胞骨格蛋白から見たアルツハイマー病のモデル動物-バッフィーコート接種実験とリン酸化の異常" 薬物精神行動. 13(6). 407- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Takeda: "Animal models for neurodegeneration in Alzheimer's disease" Annal of Psychiatry. 4(in press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Takeda: "Cytoskeletal Pathology of Alzheimer's Disease" Annal of Psychiatry. 5(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Takeda et al: "Alzheimer's Disease:Therapeutic Strategies" Giacobini,Becker eds., (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Takeda et al: "Proceedigs of the Fourth Inteational Conference on Alzheimer's Disease" K.Iqbal ed., (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2017-10-10  

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