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1992 Fiscal Year Final Research Report Summary

Development of murine models for aging brain, Senescence-Accelerated Mouse (SAM)

Research Project

Project/Area Number 02507002
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

TAKEDA Toshio  Chest Dis. Res. Inst., Kyoto Univ., Dept. of Senescence Biology, Professor, 胸部疾患研究所, 教授 (00027088)

Co-Investigator(Kenkyū-buntansha) HIGUCHI Keiichi  Chest Dis. Res. Inst.,Kyoto Univ., Dept. of Senescence Biology, Lecturer, 胸部疾患研究所, 講師 (20173156)
HOSOKAWA Masanori  Chest Dis. Red. Inst.,Kyoto Univ., Dept. of Senesce. Biology, Assoc. Prof., 胸部疾患研究所, 助教授 (00127135)
AKIGCHI Ichiro  Faculty of Med.,Kyoto Univ.,Dept. of Neurology, Assoc. Professor, 医学部, 助教授 (30115779)
MIYAMOTO Masaomi  Takeda Chem. Ing.,LTD.,Dept. I, Pharmaceutical Res.Labs.I., Chief, 第1創薬研究所, 主任研究員
Project Period (FY) 1990 – 1992
KeywordsSenescence-Accelerated Mouse (SAM) / Animal model / Senescence / Deficits in learning & memory / Brain atrophy / 脳萎縮
Research Abstract

1. Neuroaxonal dystrophic changes were observed in the nuclei fasciculi dorsalis of medulla oblongata in SAM-P/8 mice. The changes appeared earlier and progressed more rapidly in SAM-P/8 than did in SAM-R/U. beta/A4 protein-like immunoreactivity was observed in the form of granular structures(beta-LIGS) in various regions,including the medial septum, cerebral cortex, hippocampu and so on. beta-LIGS increased in number with aging, predominantly in SAM-P/8 with deficits in learning and memory.
2. The vacuolization in SAM-P/8 was marked in magnocellular reticula formation (MGRF). The severity of deficits in learning and memory closely correlated with the total area and number of vacuoles in MGRF of brain stem. Furthermore, MGRF lesioned SAM-R/1 mice showed a severe deterioration in passive avoidance tasks and an impairment in the acquisition stage of active avoidance performance. These results strongly suggest that a pathogenic role of the spongiform degeneration in brain stem in deficits in learning and memory in SAM-P/8.
3. An inbred SAM-P/10 strain has been established as a model of agerelated brain atrophy. Morphometrical studies showed that frontal cortex including prefrontal cortex, other neocortical regions, posterior piriform cortex, entorhinal cortex anterior olfactory nucleus, amygdala, and caudate putamen were atrophy-prone regions Shrinkage of the neuronal somata and loss of large neurons with age are unique for SAM-P/10, both of which bring about age-relate atrophy in cerebral cortex in SAM-P/10.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Katsuki.H.: "Age-related deterioration of lomg-term potentiation in the CA3 and CA1 regions of hippocampal slices from the senescence-accelerated mouse" Arch.Gerontol.Geriatr.11. 77-83 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Higuchi,K.: "Polymorphism of apolipoprotein A-II(app A-ii)among inbred straon of mice.Relationship between the molecular type of apo A-II and mouse senile amyloidosis" Bioch.J.279. 427-433 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda,T.: "Senescence-Accelerated Mouse(SAM):A novel murine model of accelerated senescence" J.Amer.Geriatr.Soc.39. 911-919 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimada,A.: "Inbred SAM-P/10 as a mouse model of spontaneous,inherited brain atrophy" J.Neuropathol.Exp.Neurol.51. 440-450 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimada,A.: "Age-related deterioration in conditional avoidance task in the SAM-P/10 mouse,an animal model of spontaneous brain atrophy" Brain Res.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takemura,M.: "β/A4 protein-like immunoreactive granular structures in the brain of Senescence-Accelerated Mouse(SAM)" Am.J.Pathol.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yagi,H.: "Basic,Clinical,and Therapeutic Aspects of Alzheimer's and Parkinson's Diseases" Plenum Press, 711-714 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimada,A.: "Priceedings of the 4th International Symposium on Dementia" National Center of Neurology and Psychiatry, 1-5 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsuki.H., et al: "Age-related deterioration of long-term potentiation in the CA3 and CA1 regions of hippocampal slices from the senescence-accelerated mouse" Arch. Gerontol. Geriatr.11. 77-83 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higuchi,K., et al: "Polymorphism of apolipoprotein A-II(apoA-II) among inbred strain of mice. Relationship between the molecular type or apoA-II and mouse senile amyloidosis" Bioch. J.279. 427-433 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda,T., et al: "Senescence-Accelerated Mouse(SAM) d A novel murine model of accelerated senescence" J. Amer. Geriatr. Soc.39. 911-919 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimada.A., et al: "Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy" J. Neuropathol. Exp. Neurol.51. 440-450 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimada,A., et al: "Age-related deterioration in conditional avoidance task in the SAM-P-10 mouse, an animal model of spontaneous brain atrophy" Brain Res.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takemura,M., et sl,: "beta/A4 protein-like immunoreactive granular structures in the brain of Senescence-Accelerated Mouse(SAM)" Am. J. Pathol.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiguchi,A., et al,: "Morphological changes of the brain in Senescence Accelerated Mouse(SAM-P/8) ; a newly developed memory-deficient strain" Basic, Clinical, and Therapeutic Aspects of Alzheimer's and Parkinson's Deseases, Plenum Press, New York. 697-700 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagi,H., et al: "Senescence-Accelerated Mouse SAM-P/8 shows spontaneous age- related impairment of ability of acquisition of learning and memory : An animal model of disturbances in recent memoty with aging" Basic, Clinical, and Therapeutic Aspects of Alzheimer's and Parkinson's Desease, Plenum Press, New York. 711-714 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimada,A., et al: "Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy" Proceedings of the 4th International Symposium on Dementia, National Center of Neurology and Psychiatry. 1-5 (1992)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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