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2002 Fiscal Year Final Research Report Summary

Confirmation of animal models to clarify mechanism of dementia and to develop anti-dementia drugs

Research Project

Project/Area Number 12556054
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Applied veterinary science
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

NAKAYAMA Hiroyuki  Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (40155891)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Yasuhiro  Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (80109975)
MORI Yuji  Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (40157871)
DOI Kunio  Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (70155612)
SASAKI Nobuo  Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60107414)
ONO Kenichiro  Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (50111480)
Project Period (FY) 2000 – 2002
KeywordsAnimals / fractal dimension / Senile plaques / Amyloid beta / Three-dimensinnal analysis
Research Abstract

1. Fractal dimension (FD) of senile plaques (SP) of various animal species were calculated and compared. FDs between diffuse (DP) and mature (MP) plaques were significantly different in the dog, monkey and human. In the dog. The FD value and size of SP were plotted. Significant difference was shown between the slope values of the lines of DP and MP. DP and MP were differently formed in these animals. The FD of feline DP was less than those of the dog, monkey, bear, camel and human, indicating special characteristics of feline SP.
2. SPs of aged dogs were three-dimensionally (3D) observed. An assembly of amyloid beta (A β) protein of DP was uneven nebula-like structure and that of MP was membrane-like or filamentous one. There were areas of low-density A β deposition inside DP and MP. 3D distribution of amyloid precursor protein, ubiqiutin, glial fibrillary acidic protein and neurofilament were also examined, The results indicated that the two types of SP are formed separately.
3. 3D pattern and fractal dimension of assemblies of the two A/β subspecies, I.e. A/β40 and A β42, were investigated. The processes of the 2 types of A β were clarified to be different.
4. The distribution of presenilin 1 (PS1) protein in the brain of the eynomoIgus monkey was examined. Carboxyl terminal of PS1 was detected in the cortical neuropil and the deposition was increased with age. The results of the present studies revealed the brain lesions of aged animals. Further, important paradigms in the field of comparative biology such as "SPs are formed but neurofibrilliary tangles are not formed in the nonhuman animals" have been clarified.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Nakayama, H., Yoshikawa, Y., Doi, K.他: "Fractal analysis of senile plaque observed in various animal species"neuroscience letters. 297. 195-198 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyawaki, K., Nakayama, H., Nakamura, S., Doi, K.: "Three-dimensional structures of canine senile plaques"Acta Neuropathologica. 102. 321-328 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura, N., Nakayama, H., Doi, K., Yoshikawa, Y.他: "Age-related changes in the localization of presenilin-1 in cynomolgus monkey brain"Brain Research. 922. 30-41 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyawaki, K., Nakayama, H., Doi, K.: "Three-dimentional and fractal analyses of assemblies of amyloid β protein subtypes [Aβ 40 and Aβ 42(43)] in canine senile plaques"Acta Neuropatholoiga. 103. 228-236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Samura, E., Nakayama, H., Doi, K., Yoshikawa, Y.他: "Biological and immunohistochemical studies of amyloid β protein (Aβ) species in aged canine brains"Brain Research. (投稿準備中). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中山裕之: "老齢性脳病変の進化病理学的考察-動物に神経変性疾患はあるのか-"獣医神経病(実際の発刊は2002年). 第8号. 3-9 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中山裕之: "イヌに痴呆はありますか?"Clinical Neuroscience(臨床神経科学). 第20巻. 487 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayama, H., Yoshikawa, Y., Doi, K. et al: "Fractal analysis of senile plaques observed in various animal species"Neuroscience Letters. 297. 195-198 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyawaki, K., Nakayama, H., Nakamura, S., Doi, K. et al: "Three-dimensional structures of canine senile plaques"Acta Neuropathologica. 102. 321-328 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, N., Nakayama, H., Doi, K., Yoshikawa, Y. , et al: "Age-related changes in the localization of presenilin-1 in cynomolgus monkey brain"Brain Research. 922. 30-41 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyawaki,K., Nakayama, H., Doi, K., et al: "Three-dimensional and fractal analyzes of assemblies of amyloid β protein subtypes [A β 40 and A β 42(43)] in canine senile plaques"Acta Neuropathologica. 103. 228-236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Samura.E., Nakayama,H., Doi,K., Yoshikawa,Y., et al: "Biological and immunohistochemical studies of amyloid β protein (A β) species in aged canine brains"Brain Research. in preparation.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayama, H.: "An evolutionary study of age-related brain pathology―Are neurodegenerative diseases present in nonhuman anirnals ?"Journal of Japanese Veterinary Neurology (In Japanese). 8. 3-9 (2001)

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

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Published: 2004-04-14  

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