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2006 Fiscal Year Final Research Report Summary

Role of actin cytoskeleton in the axonal growthcone during brain development

Research Project

Project/Area Number 16300117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University

Principal Investigator

SHIRAO Tomoaki  Gunma University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF NEUROBIOLOGY AND BEHAVIOR, PROFESSOR (20171043)

Co-Investigator(Kenkyū-buntansha) YAMAZAKI Hiroyuki  Gunma University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF NEUROBIOLOGY AND BEHAVIOR, Research Associate (10334137)
HANAMURA Kenji  Gunma University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF NEUROBIOLOGY AND BEHAVIOR, Research Associate (40361365)
SHKINO Yuko  UNIVERSITY OF TOKYO, INSTITUTE OF MEDICAL SCIENCE, DIVISION OF NEURONAL NETWORK, ASSOCIATE PROFESSOR (70138866)
KOJIMA Nobuhiko  Gunma University, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF NEUROBIOLOGY AND BEHAVIOR, Assistant professor (80215251)
Project Period (FY) 2004 – 2006
Keywordsactin / growthcone / hippocampal neuronal culture / immunofluorescence staining / actin-binding proteins / axonal growth / microtubule / 微小管
Research Abstract

During the neuronal network formation, the inhibition of axonal growthcone morphogenesis and its function make it impossible for the brain function to develop normally. In this study, in order to elucidate the regulatory mechanism of actin cytoskeleton, which is directly involved in the morphogenesis and function of axonal growthcones, we focused in the actin filament and analyzed the change in the protein network of actin-binding proteins which regulate the physicochemical and biochemical characters using primary cultured hippocampal neurons. We first analyzed the distribution of drebrin in the axonal growthcone of cultured hippocampal neurons at various developmental stages using immunocytochemistry. In the neuron of stage 2, drebrin was localized at transitional area of growthcones. The immunocytochemistry also showed that Neurabin 1 showed similar localization of in the growthcone to drebrin. We further analyzed localization of various actin-related proteins in the growthcones at stage 2. Microtubules did not invade into the transitional area. In order to discriminate drebrin E from drebrin A, we developed drebrin A-specific antibody. This antibody clearly showed that growthcone only has drebrin E. This antibody further showed that migrating neurons in the adult brain only express drebrin E. We developed the new identification method of migrating neurons in the adult brain. Using this method, we discovered migrating neurons in the piriform cortex in adult rats. We finally showed that drebrin knockdown by RNAi resulted the inhibition of axonal growth.

  • Research Products

    (30 results)

All 2007 2006 2005 Other

All Journal Article (30 results)

  • [Journal Article] Expression of drebrin E in migrating neuroblasts in adult rat brain:Coincidence between drebrin E disappearance from cell body and cessation of migration2007

    • Author(s)
      Song M, Shirao T, et. al.
    • Journal Title

      Neuroscience

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precedes the onset of Alzheimer's disease pathology in double knock-in mice2007

    • Author(s)
      Aoki C, Shirao T, et. al.
    • Journal Title

      J.Comp.Neurol. 505

      Pages: 352-362

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Roie of actin cytoskeleton in dendritic spine morphogenesis2007

    • Author(s)
      Sekino.Y, Kojima N, Shirao T.
    • Journal Title

      Neurochem.Int. 51

      Pages: 92-104

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Drebrin A content correlates with spine head size in the adult mouse cerebral cortex2007

    • Author(s)
      Kobayashi C, Shirao T., et. al.
    • Journal Title

      J.Comp.Neurol. 503

      Pages: 618-626

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Many faces of Drebrin:from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes2007

    • Author(s)
      Majoul, I, Shirao T, et. al.
    • Journal Title

      Histochem.Cell Biol. 127

      Pages: 355-361

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex:the study of neurological disorders accompanied by cognitive deficits2007

    • Author(s)
      Kojima, N., Shirao, T.
    • Journal Title

      Neurosci.Res. 58

      Pages: 1-5

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Increase of AMPA receptors-mediated miniature EPSC amplitude after chronic NMDA receptor blockade in cultured hippocampal neurons2007

    • Author(s)
      Kato K, Shirao T, et. al.
    • Journal Title

      Neurosci.Lett. 418

      Pages: 4-8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precedes the onset of Alaheimer's disease pathology in double knock-in mice2007

    • Author(s)
      Aoki C, Shirao T, et. al.
    • Journal Title

      J.Comp.Neurol. 505

      Pages: 352-362

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Many faces of Drebrin : from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes2007

    • Author(s)
      Majoul, I., Shirao, T., Sekino, Y., Duden, R.
    • Journal Title

      Histochem. Cell Biol. 127

      Pages: 355-361

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex : the study of neurological disorders accompanied by cognitive deficits.2007

    • Author(s)
      Kojima, N., Shirao, T.
    • Journal Title

      NeurosclNeurosci Res. 58

      Pages: 1-5

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increase of AMPA receptors-mediated miniature EPSC amplitude after chronic NMDA receptor blockade in cultured hippocampal neurons2007

    • Author(s)
      Kato, K., Sekino, Y., Takahashi, H., Yasuda, H., Shirao, T.
    • Journal Title

      Neurosci. Lett 418

      Pages: 4-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Drebrin A content correlates with spinc head size in the adult mouse cerebral cortex2007

    • Author(s)
      Kobayashi, C., Aoki, C., Kojima, N., Yamazaki, H., Shirao, T.
    • Journal Title

      J. Comp. Neurol. 503

      Pages: 618-626

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of actin cytoskeleton in dendritic spine morphogenesis2007

    • Author(s)
      Sekino Y, Kojima N, Shirao T.
    • Journal Title

      Neurochem. Int. 51

      Pages: 92-104

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precedes the onset of Alzheimer's disease pathology in double knock-in mice2007

    • Author(s)
      Aoki C, Mahadomrongkul V, Fujisawa S, Habersat R, Shirao T.
    • Journal Title

      J. Comp. Neurol. 505

      Pages: 352-362

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution:disappearance from dendritic spines and appearance in dendritic shafts2006

    • Author(s)
      Sekino Y., Shirao T., et. al.
    • Journal Title

      Mol.cell.Neurosci. 31

      Pages: 493-504

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Downregulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurons2006

    • Author(s)
      Takahashi, H, Shirao T, et. al.
    • Journal Title

      J.Neuochem 97(sl)

      Pages: 110-115

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Invivo,competitive blockade of NMDA receptors induces rapid shape change of post-synaptic spines and F-actin reorganization within dendritic spines of adult rat cortex2006

    • Author(s)
      Fujisawa, S., Shirao, T., Aoki, C.
    • Journal Title

      Neuroscience 140

      Pages: 1177-1187

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] AMPA receptor downscaling at the onset of Alzheimer's pathology in double knock-in mice2006

    • Author(s)
      Chang EH, Shirao T, et. al.
    • Journal Title

      Proc.Natl.Acad.Sci.(USA) 103

      Pages: 3410-3415

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro2006

    • Author(s)
      Shirai K, Shirao T, et. al.
    • Journal Title

      Neurosci.Lett. 399

      Pages: 57-60

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution : disappearance from dendritic spines and appearance in dendritic shafts2006

    • Author(s)
      Sekino, Y., Tanaka, S., Hanamura, K., Yamazaki, H., Sasagawa, Y., Xue Y., Hayashi, K., Shirao, T.
    • Journal Title

      MoL Cell. Neurosci 31

      Pages: 493-504

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Downregulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurons2006

    • Author(s)
      Takahashi, H., Mizui T., Shirao, T.
    • Journal Title

      J. Neuochem 97(sl)

      Pages: 110-115

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In vivo, competitive blockade of NMDA receptors induces rapid shape change of post-synaptic spines and F-actin reorganization within dendritic spines of adult rat cortex.2006

    • Author(s)
      Fujisawa, S., Shirao, T., Aoki, C.
    • Journal Title

      Neuroscience 140

      Pages: 1177-1187

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] AMPA receptor downscaling at the onset of Alzheimer's pathology in double knock-in mice2006

    • Author(s)
      Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul, V., Shirao, T., Aoki, C., Huerta, P.T.
    • Journal Title

      Proc. Natl. Acad Sci.(USA) 103

      Pages: 3410-3415

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential effects of x-irradiation on immatur and mature hippocampal neurons in vitro.2006

    • Author(s)
      Shirai, K., Mizui, T., Suzuki, Y., Kobayashi, Y., Nakano, T., Shirao, T.
    • Journal Title

      Neurosct Lett. 399

      Pages: 57-60

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia,and the formation of large abnormal protrusions2005

    • Author(s)
      Mizui T., Shirao T., et. al.
    • Journal Title

      Mol.Cell.Neurosci. 30

      Pages: 149-157

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PSl genes2005

    • Author(s)
      Mahadomrongkul, V, Shirao T, et. al.
    • Journal Title

      Brain Res. 1064

      Pages: 66-74

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Drebrin A is a Postsynaptic Protein that Localizes in vivo to the Submembranous Surface of Dendritic Sites Forming Excitatory Synapses2005

    • Author(s)
      Aoki, C., Sekino, Y., Hanamura, K., Fujisawa, S., Mahadomrongkul, V., Ren, Y., Shirao, T.
    • Journal Title

      J. Comp. Neurol. 483

      Pages: 383-402

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions.2005

    • Author(s)
      Mizui, T., Takahashi, H., Sekino, Y., Shirao. T.
    • Journal Title

      Mol. Cell. Neurosci. 30

      Pages: 149-157

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes2005

    • Author(s)
      Mahadomrongkul, V., Huerta, P. T., Shirao, T., Aoki, C.
    • Journal Title

      Brain Res. 1064

      Pages: 66-74

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of drebrin E in migrating neuroblasts in adult rat brain : coincidence between drebrin E disappearance from cell body and cessation of migration

    • Author(s)
      Song M, Kojima N, Hanamura K, Sekino Y, Inoue KH, Mikuni M, Shirao T
    • Journal Title

      Neuroscience. (印刷中)

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

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Published: 2010-02-04  

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