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Comparative evolutionary studies on the expmssion of dementia-related genes in aging nonhuman animals

Research Project

Project/Area Number 14360188
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

NAKAYAMA Hiroyuki  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 (40155891)

Co-Investigator(Kenkyū-buntansha) 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)
UETSUKA Koji  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assistant, 大学院・農学生命科学研究科, 助手 (60251419)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsAmyloid beta / APP / Computer / Mammals / Brain / Microarray / Aging / Senile plaques / 老人班
Research Abstract

We examined the immunohistochemical localization of beta-amyloid (A beta) and beta-amyloid precursor protein (APP) in the neuronal and non-neuronal tissues of dogs. A beta was detected only in the senile plaque (SP) in cerebrum of aged dogs. APP was expressed in the neuronal cell body and fiber independent of the age. In addition, glandular epithelial cells were immunopositive for APP. Thus, it is suggested that APP may be expressed in the non-neuronal epithelial tissues in dogs.
Gene expressions of the canine brain was investigated using array membrane filters prepared for human analysis. Brain aging-related genes were upregulated in the brain from aged dogs. However, the expression of the APP gene was not increased in the aged brains.
An attempt to create SPs of various shapes in silica was performed, using computer software programs. The resultant structures were morphologically evaluated by the fractal dimension (FD) method. SPs with low FD seemed to be smaller in size and less dense than those with higher FD. The low-FD SPs in silico may correspond to feline SPs in vivo, and the high-FD SP in silico to SPs of other animal species. According to the present results, SP formation in the aged feline brain may be different from that of other animal species, indicating a special A beta deposition process in cats.
APP may play an important function(s) in the brain and some glandular tissues, and may be abnormally degraded to A beat in the brain by aging in dogs. However, the expression of APP was stable during life. Such abnormal degradation of APP and the inhibition of A betalysis may be crucial for A beta deposition in the canine brain.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (18 results)

All 2004 2003 2002 2001 Other

All Journal Article (14 results) Publications (4 results)

  • [Journal Article] A comparative study of age-related brain pathology - Are neurodegenerative diseases present in nonhuman animals? -2004

    • Author(s)
      Nakayama, H., Uchida, K., Doi, K.
    • Journal Title

      Medical Hypotheses 68

      Pages: 196-202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunohistochemical detection of β-amyloid and β-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues.2004

    • Author(s)
      Fukuoka, N, Nakayama, H., Doi, K.
    • Journal Title

      Amyloid 11

      Pages: 173-178

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Age-dependent susceptibility to MPTP neurotoxicity in C57BL mice : A tyrosine hydroxylase-immunohistochemical evaluation.2004

    • Author(s)
      He, X.J., Nakayama, H., Ueno, M., Doi, K.
    • Journal Title

      J.Toxicol.Pathol. 17

      Pages: 239-244

    • NAID

      10025852320

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A comparative study of age-related brain pathology -A neurodegenerative diseases present in nonhuman animals?-2004

    • Author(s)
      Nakayama, H., Uchida, K., Doi, K.
    • Journal Title

      Med.Hypotheses 63

      Pages: 198-202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunohistochemical detaction of beta-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues2004

    • Author(s)
      Fukuoka, A., Nakayama, H., Doi, K.
    • Journal Title

      Amyloid 11

      Pages: 173-178

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Agedependent susceptibility to MPTP neurotoxicity in C57BL mice : A tyrosine hydroxylase-immunohistochemical evaluation.2004

    • Author(s)
      He, X.J., Nakayama, H., Ueno, M., Doi, K.
    • Journal Title

      J.Toxicol.Pathol. 17

      Pages: 239-244

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A comparative study of age-related brain pathology-Are neurodegenerative diseases present in nonhuman animals? -2004

    • Author(s)
      Nakayama, H., Uchida, K., Doi, K.
    • Journal Title

      Medical Hypotheses 63

      Pages: 198-202

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immunohistochemical detection of β-amyloid and β-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues.2004

    • Author(s)
      Fukuoka, A., Nakayama, H., Doi, K.
    • Journal Title

      Amyloid 11

      Pages: 173-178

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Age-related histological changes in the canine substantia nigra.2003

    • Author(s)
      Uchida, K., Kihara, N., Hashimoto, K., Nakayama et al.
    • Journal Title

      J.Vet.Med. Sci 65

      Pages: 179-185

    • NAID

      110003886170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Age-related histological changes in the canine substantia nigra.2003

    • Author(s)
      Uchida, K., Kihara, N., Hashimoto, K., Nakayama, H., Yamaguchi, R., Tateyama, S.
    • Journal Title

      J.Vet.Med.Sci. 65

      Pages: 179-185

    • NAID

      110003886170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] イヌに痴呆はありますか?2002

    • Author(s)
      中山裕之
    • Journal Title

      Clinical Neuroscience(臨床神経科学) 第20巻

      Pages: 487-487

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Do dogs show dementia? (in Japanese)2002

    • Author(s)
      Nakayama, H.
    • Journal Title

      Clinical Neuroscience 20

      Pages: 487-487

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 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-2001

    • Author(s)
      中山裕之
    • Journal Title

      獣医神経病(実際の発刊は2002年) 第8号

      Pages: 3-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evolutional pathological discussion of senile brain lesions -Are there neurodegenerative disorders in animals?-(in Japanese)2001

    • Author(s)
      Nakayama, H.
    • Journal Title

      Juui Shinkeibyou No.8(published in 2002)

      Pages: 3-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nakayama, H., Uchida, K., Doi, K.: "A comparative study of age-related brain pathology - Are neurodegenerative diseases present in nonhuman animals? -"Medical Hypotheses. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuoka, A., Nakayama, H., Doi, K.: "Immunohistochemical detection of β-amyloid and β-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues."Amyloid. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [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. 第8号(実際の発刊は2002年). 3-9 (2001)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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