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アルツハイマー病脳老人斑のApolipoproteinE産生細胞とその制御

Research Project

Project/Area Number 12878146
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Nerve anatomy/Neuropathology
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

内原 俊記  財団法人東京都医学研究機構, 東京都神経科学総合研究所, 研究員 (10223570)

Co-Investigator(Kenkyū-buntansha) 中村 綾子  財団法人東京都医学研究機構, 東京都神経科学総合研究所, 研究員 (90301796)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsApolipoprotein E / 老人斑 / 脳梗塞 / 神経修復 / Balooned neuron / アポリポプロテインE / 老人班 / Peptide nucleic acid / in situ hybridization / Peptide Nucleic Acid
Research Abstract

中枢神経系でのapolipoproteinE(ApoE)産生細胞は従来astrocyteとかんがえられてきたが、脳梗塞層周辺では神経細胞やミクログリアに強いApoE様免原性がみられることを初めてあきらかにした。また脳梗塞脳のウエスタンブロットでApoEの発現量を比較すると、正常対象やアルツハイマー病脳に比較しても脳梗塞脳ではApoEの発現量が有意に多いことを定量的に確認した。培養したneuroblastoma cell lineにストレス刺激を加えるとApoE蛋白の発現が上昇することを定量的に確認し、脳梗塞でのApoE陽性神経細胞に対応する所見と思われる。以上より他の細胞からのシグナルが無くても神経細胞はApoE産生を亢進させ得ることが確認され、神経細胞の障害からの回復過程にApoEの発現上昇が関与していることが示唆される(以上Stroke in press)。ApoEは脳梗塞に見られるballooned neurons(BNs)にも集積しているが、変性疾患にみられるBNsはその免疫原性に乏しい点で異なり、変性過程では障害が持続的で回復傾向に乏しいとすると解釈できる。
技術的には蛍光多重染色に改良を加え、様々なエピトープの相互関係を人剖検脳にみられる病変を対象に検討した。今後アルツハイマー病脳においてApoEの発現細胞を同定し、病変との関連を明らかにする。

Report

(3 results)
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Aoki K, Uchihara T, Sanjo N, Nakamura A, Ikeda K, Tsuchiya K, Wakayama Y: "Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction"Stroke. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibuya K, Uchihara T, Nakamura A, Ishiyama M, Yamaoka K, Yagishita S: "Reversible conformational change of tau-2 epitope exposed to detergent in glial cytoplasmic includions in multiple system atrophy"Acta Neuropathol. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kumada S, Uchihara T, Hayashi M, Nakamura A, Kikuchi E, Mizutani T, Oda M: "Promyelocytic leukemia protein is redistributed during the formation of intranuclear inclusions independent of polyglutamine expansion : an immunohistochemical study on Marinesco bodies"J Neuropathol Exp Neurol. 68. 984-991 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakamoto M, Uchihara T, Hayashi M, Nakamura A, Kikuchi E, Mizutani T, Mizusawa H, Hirai S: "Heterogeneity of nigral and cortical Lewy bodies differentiated by amplified triple-labeling for alpha-synuclein, ubiquitin, and thiazin red"Exp Neurol. 177. 88-94 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchiya K, Takahashi M, Miyazaki H, K, Uchihara T, Tominaga I, Nakano I 他: "Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia : a clinicopathological study of eight autopsy cases"Acta Neuropathol. 104. 249-259 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshiki Uchihara, Ayako Nakamura, Utako Nagaoka et al.: "Dual enhancement of double immunofluorescent signals by CARD :"Histochem Cell Biol. 114. 447-451 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi J, Tanaka J, Arai K, Funata N, Uchihara T: "Recrutment of nonexpanded polyglutamine proteins to llthauuclea aggregates un NIHID"J. Neuropathol Exp Neurol. 60. 369-376 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchihara T, Nakamura A, Yamazaki M, Mori O: "Evolution from pretangle neurons to NFT monitored by thiazin red"Acta Neuropathol. 101. 535-539 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchihara T, Nakamura A, Yamazaki M, Mori O et al.: "Different conformation of neuronal Tau depodsits distinguished by double immunofluorescence"Acta Neuropathol. 102. 462-466 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内原俊記: "神経系でのアポE産生細胞の同定とその制御 伊藤正男, 川合述史編 ブレインサイエンス・レビュー2001"(財)ブレインサイエンス振興財団. 11 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi J,-(他5名)-Uchihara T: "Recruitment of nou-expanded polyglutamine proteins in intranuclear hyaline inclusion disease"J Neuropathol Exp Neurol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchihara T 他5名: "Non-expanded polyglutamine proteins into intranuclear inclusions of hereditary ataxias"Acta Neuropathol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchihara T 他3名: "Evolution from pretangle neurous to neurofibrillary tangles"Acta Neuropathol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchihara T 他3名: "Dual enhancement of double immunofluorescent signals by CARD"Histochem Cell Biol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchihara T 他3名: "Tau-positive neurous in CBD and AD"Acta Neuropathol. 100. 385-389 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Uchihara T 他3名: "Appearance of Tau-2 immunoreactivity in glial cells in human brain with cerebral infarction"Neurosci Lett. 286. 99-102 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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