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Relationship between neurodegenerative diseases and neurofilaments accumulated in somata and/or axons

Research Project

Project/Area Number 12680741
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionCollege of Nutrition, Koshien University

Principal Investigator

GOTOW Takahiro  Koshien University, College of Nutrition, Professor, 栄養学部, 教授 (20135693)

Co-Investigator(Kenkyū-buntansha) UCHIYAMA Yasuo  Osaka University, Graduate School of Medicine, Department of Cell Biology and Anatomy, Professor, 大学院・医学系研究科, 教授 (10049091)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsNeurofilament / crossbridge / NF-L knockout mice / NF-M knockout mice / NF-H knockut mice / NF-M tailless mice / NF-H tailless mice / Double tailless mice / ニューロフィラメント遺伝子操作マウス / NF-MC末端欠損ノックインマウス / NF-HC末端欠損ノックインマウス / NF-M, NF-H両C末端欠損ノックインマウス / 軸索機脳障害 / 神経細胞 / NF-L欠損マウス / NF-H欠損マウス / 軸索輸送障害 / 急送凍結ディープエッチ電顕法
Research Abstract

Abnormal neurofilament (NF) accumulation in neuronal somata and/or axons is seen in some of neurodegenerative diseases, such as amyotrophic lateral sclerosis, in demyelinated diseases, in mice overexpressing exogenous NF gene, and in aged animals including human. The fact that the transgenic mice overexpressing the NF gene show neuronal degeneration suggests that the abnormal NF accumulation is related with the mutation or alteration in the NF genes. To clarify the mechanism of NF accumulation, we made knockout mice devoid of each NF subunit gene and analysed them with biochemical and morphological methods. We also made knockin mice, in which NF-M, NF-H or both genes were replaced to delete their carboxy-terminal tail domains, to know how the absence of crossbridges influence the NF organization or neuronal structure. In all transgenic mice, alterations in structure and/or cytoskeletal organization were detectable predominantly in the axonal compartment. NF-L knockout mice showed expre … More ssions of NF-M and NF-M mRNAs but hardly those of their proteins, resulting in absence of NFs and reduction of axonal calibers, but increase in density of microtubules. NF-M knockout mice showed a reduced expression of NF-L protein, and their NFs were decreased in number and irregular. NF organization was almost unchanged in NF-H knockout mice, in which NF- M protein was increased in amount. Although selective deletion of the NF-M tail had no significant change in NF organization, similar loss of NF-H tail had significant reduction of crossbridges and more compaction of core filaments. Deletion of both tails showed reduction of axonal calibers and significant change in axoplasmic organization, i.e., core filaments were irregular with complete absence of crossbridges, sometimes occupied with membrane-bound organelles, indicating impairment of the axonal transport. There were increases in both size and density of mitochondria when the axonal calibers were reduced. Taken together, abnormal accumulation of NFs in the neurons may be prevented by the NF gene theraphy. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nakamura, H.: "Protective effects of cocoa water soluble dietary fiber and defatted cocoa on gastric mucous membrane in rats"Bull.Koshien Univ.. 28. 33-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gotow, T.: "Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells"Cell Death Differ.. 7. 666-674 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sato, M.: "Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex"J.Mol.Biol.. 300. 421-431 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashimoto, R.: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation"J.Neurochem.. 75. 373-382 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gotow, T.: "Neurofilaments in health and disease"Med.Electron Microsc.. 33. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Linden, M.: "Effects of desmin gene knockout on mice heart mitochondria"J.Bioenerg.Biomembr.. 33. 333-341 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura, H., Asayama, S., Osada, H., Yoshizawa, M., Gotow, T.: "Protective effects of cocoa water soluble dietary fiber and defatted coca on gastric mucous membrane in rats"Bull. Koshien Univ. 28. 33-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gotow, T.Shibata, M., Kanamori, S., Tokuno, O., Ohasawa, Y., Sato, N., isahara, K., Yayoi, Y., Watanabe, T., Leterrier, J.F., Linden, M., Komonami, E., Uchiyamama, Y.: "Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells"Cell Deat Differ. 7. 666-674 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sato, M., Gotow, T., You, Z., Komamura-Kohno, Y., Uchiyama, Y., Yabuta, N., Nojima, H., Ishimi, Y.: "Electron microscopic observation and single-stranded DNA binding activity of the Mcm4, 6, 7 complex"J. Moi. Biol. 300. 421-431 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hashimoto, R., Nakamura, Y., Komai, S., Kashiwagi, Y., Tamura, K., Gotow, T., Aimoto, S., Kaibuchi, K., Shiosaka, S., Takeda, M: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation"J. Neurochem. 75. 373-382 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gotow, T: "Neurofialaments in health and disease"Med. Electron Microsc. 33. 173-199 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Linden, M., Li, Z., Paulin, D., Gotow, T., Leterrier, J.-F: "Effects of desmin gene knockout on mice heart miltochondria"J. B ioenerg. Biomembr. 33. 333-341 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gotow, T.: "Neuro-filaments in health and disease"Medical Electron Microscopy. 33. 173-199 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Linden, M.: "Effects of desmin geneknockout on mice heart mitochondria"Journal of Bionergetics and Biomembranes. 33. 333-341 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gotow,T.: "Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells"Cell Death and Differentiation. 7. 666-674 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato,M.: "Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex"Journal of Molecular Biology. 300. 421-431 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hashimoto,R.: "Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulln-dependent protein kinase II in the apical dendrites during long-term potentiation"Journal of Neurochemistry. 75. 373-382 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gotow,T.: "Neurofilaments in health and disease"Medical Electron Microscopy. (in press).

    • Related Report
      2000 Annual Research Report

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

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