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Making an animal model of dementia for studying a pathophysiology and recovery process of dementia.

Research Project

Project/Area Number 01570609
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionKochi Medical School

Principal Investigator

IKEDA Hisao  Kochi Medical School, Department of Neuro-psychiatry, Professor, 医学部, 教授 (90033076)

Co-Investigator(Kenkyū-buntansha) OKADA Michiyuki  Kochi Medical School, Department of Neuro-psychiatry, Assistant, 医学部, 助手 (20224024)
YAMASHITA Motoshi  Kochi Medical School, Department of Neuro-psychiatry, Instructor, 医学部, 講師 (30174684)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
KeywordsDementia / Animal model of dementia / Medial septum lesion / Basal nucleus lesion / 8-aum radial maze / Water maze / アルツハイマ-型老年痴呆 / 水迷路課題
Research Abstract

In order to establish the experimental systems for studying a pathophysiology and recovery process of dementia, many kinds of neurotoxic drugs for making a lesion in the cholinergic systems in the brain, and tasks for evaluating the learning ability of an animal were studied with the following results.
Hypofunction of cholinergic systems as a neurochemical finding and spatial disorientation as a clinical symptoms are well known characters of Alzheimer's disease. These findings were reproduced in animals to make an animal model of dementia.
Ibotenic acid or AF64A were injected into medial septum (MS) or nucleus basalis of Magnocellularis (NBM). The effects of cholinergic hypofunction on spatial memory were assessed in water maze (Morris, 1981). After injection of ibotenic acid into NBM, escape latency was significantly increased. Transfer test also showed significant increase of time to stay in the area where platform was once placed. MS lesion combined with unilateral lesion of NBM by AF64A significantly increased escape latency. And furthermore, escape latency was longer after 24 hour interval compared to ten minutes interval. These results show the function of MS cholinergic system in long term and short term memory. Even unilateral lesion of NBM significantly impaired acquisition of spatial memory.
To our knowledge, radial maze task was a potent task to assess MS cholinergic hypofunction but was not a potent task to assess NBM cholinergic hypofunction. But these results showed that water maze is a useful task to access, especially NBM cholinergic system.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 池田 久男: "痴呆の病態生理(シンポジウム)" 第14回 日本生物学的精神学会抄録. 53 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ikeda,H.: "Vasoactive intestinal polypeptide presynaptically enhances the synaptic transmission in cultured sympathetic neurons" Brain Research. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 山下 元司: "Choline系機能低下による痴呆モデル動物の空間記憶障害 ー 特に水迷路試験について" 脳と精神の医学. 2. 338-342 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamashita,M.: "The role of two major cholinergic systems in memory acquisition and retention in the eight - arm radial maze" Int.J.Geriatric Psychiat.7. (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 山下 元司: "前脳基底部および中隔野損傷ラットの学習記憶障害における相違 ー水迷路課題を用いての検討ー" 老年精神医学雑誌. 2. 771-776 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okada,M.: "Central depletion of dopamine in rats by 1-mental-4-phenylpyridine" Life Sciences. 45. 391-399 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 池田 久男: "神経ペプチドの基礎と臨床" 祖父江逸郎編, 49-52 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mie Takahashi, Masaharu Ogawa, Hitoshi Ohta and Hisao Ikeda: "Vasoactive intestinal polypeptide presynaptically enhances the synaptic transmission in cultured sympathetic neurons." Brain Research. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ritsu Yamasaki, Motoshi Yamashita, Koshiro Taguchi, Michiyuki Okada and Hisao Ikeda: "The role of two major cholinergic systems in memory acquistition and retention in the eight-arm radial maze." Int. J. Geriat. Psychiat.7. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yasunobu Masuda, Toyohiko Kokubu, Motoshi Yamashita, and Hisao Ikeda: "Spatial memory inpairment following basal forebrain or medial septum lesion in Morris water maze." J. of Geriat. Psychiat. 2. 771-776 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Michiyuki Okada, Kunihiko Yokotani, Motoshi Yamashita, Hisao Ikeda and Yoshitsugu Osumi: "Central depletion of dopamine in rats by 1-mental-4-phenylpyridine." Life Science. 45. 391-399 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 池田 久男: "痴呆の病態生理(シンポジウム)" 第14回日本生物学的精神学会抄録. 53 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ikeda,H.: "Vasoactive intestinal polypeptide presynaptically enhances the synaptic transmission in cultured sympathetic neurons" Brain Research. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 山下 元司: "Choline系機能低下による痴呆モデル動物の空間記憶障害ー特に水迷路試験について" 脳と精神の医学. 2. 338-342 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamashita,M.: "The role of two major cholinergic systems in memory acguisition and retention in the eight‐arm radial maze" Int.J.Geriatric Psychiat.7. (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 山下 元司: "前脳基底部および中隔野損傷ラットの学習記憶障害における相違ー水迷路課題を用いての検討ー" 老年精神医学雑誌. 2. 771-776 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 池田 久男: "神経ペプチドの基礎と臨床" 祖父江逸郎編, 49-52 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 池田 久男: "前脳基底部および中隔野損傷ラットの学習記憶障害における相違ー水迷路課題を用いての検討ー" 老年精神医学雑誌. 2. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 山下 元司: "前頭基底部および中隔野損傷ラットの実習・記憶障害における相違ー特に水迷路課題についてー" 神経化学. 29. 440-441 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 山下 元司: "Choline系機能低下による痴呆モデル動物の空間記憶障害ー特に水迷路試験についてー" 脳と精神の医学. 2. 338-342 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Okada,M.: "Central depletion of dopamine in rats by 1ーmethylー4ーphenylpyridine" Life Sciences. 45. 391-399 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 池田 久男: "脳コリン系損傷ラットの学習記憶におよぼすビタミンB_<12>とリン脂質の影響" 第9回日本痴呆学会抄録. 14 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ikeda,H.: "Nucleus basalis of magnocellularis and medical septum lesions and differentiations of performance in eight arms radial mage task." Experimental Neurology.

    • Related Report
      1989 Annual Research Report
  • [Publications] 池田久男: "イボテン酸によるNucleus Basalis of Magnocellularis破壊による学習記憶障害モデル動物作成の試み" 神経化学. 27. 234-235 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 山本元司: "局所投与したコリン毒AF64Aの長期効果の検討" 神経化学. 26. 598-600 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] 山下元司: "選択的choline毒AF64Aを用いた痴呆モデル動物の研究" 精神薬療基金年報. 18. 31-37 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] 池田久男: "Medical septal area破壊による空間記憶障害動物の作成" Dementia. 1. 229-237 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ikeda,H.: "Neurochemical effects following AF64A injection into the basal nuclei of rats" The Japanese J.of Psychiatry and Neurology. 41. 756-762 (1987)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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