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Molecular pathology of neuronal differentiation, migration and death in developmental disorders.

Research Project

Project/Area Number 08670933
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionJichi Medical School

Principal Investigator

MIZUGUCHI Masashi  Jichi Medical School, Dept.Pediatrics, Associate Professor, 医学部, 助教授 (20209753)

Co-Investigator(Kenkyū-buntansha) TAKASHIMA Sachio  National Institute of Neuroscience, NCNP,Director, 神経センター神経研究所, 部長 (70038743)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsBak / Tuberous sclerosis / Miller-Dieker syndrome / Apoptosis / Tuberin / PAF / PAF acetylhydrolase
Research Abstract

A.Neuronal death
We produced a polyclonal antibody against Bak, a protein promoting neuronal apoptosis, and thereby studied its expression in human brains by Western blotting and immunostaining. In 1996, we investigated the changes associated with development and aging, and demonstrated that the expression of Bak is high in the fetal and aged brains. In 1997, we comapared Bak immunoreactivity between Down syndrome and control patients. In Down syndrome brains, the aging-related upregulation of Bak occurred prematurely. Cerebral neurons became Bak-positive prior to the development of neurofibrillary changes.
B.Neuronal differentiation
We produced rabbit antibodies against the N-and C-terminal of tuberin, the product of the TSC2 gene responsible for tuberous sclerosis. In 1996, we demonstrated the expression of tuberin in control cerebra. During development, tuberin content increased with age. Tuberous sclerosis brains by contrast showed loss of tuberin, which was severe in both the hamartomatous lesions (cortical tuber and subependymal giant cell tumor) and histologically normal cortices. Tuberin immunoreactivity was also lost from the renal and cardiac hamartomas. In 1997, we observed a normal level of tuberin expression in focal cortical dysplasia, thereby indicating pathophysiological difference between tuberous sclerosis and cortical dysplasia.
C.Neuronal migration
We extended immunohistochemical studies of the LIS1 gene product (a 45k subunit of PAF acetylhydrolase), the defect of which being responsible for the Miller-Dieker lissencephaly syndrome. In 1996, we studied the expression of LIS1 in various migration disorders, and demonstrated that the loss of LIS1 is specific to the syndrome. In 1997, we immunostained human fetal brains and observed strong labeling of the ventricular neuroepithlium and Cajal-Retzius cells.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report

Research Products

(26 results)

All Other

All Publications

  • [Publications] Mizuguchi M, et al.: "Tuberin loss from cerebral tissues-Reply." Annals of Neurology. 47(2). 271-272 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M, et al.: "Tuberin immunohistochemistry in brain,kidneys and heart with or without tuberous sclerosis." Acta Neuropathologica. 94(5). 532-538 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Clark GD, et al.: "Predominant localization of the LIS family of geneproducts to Cajal-Retzius cells and ventricular neuroepithelium in the developing human cortex." Journal of Neuropathology and Experimental Neurology. 56(9). 1044-1052 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iwama H, et al.: "Depletion of cerebral D-serine in non-ketotic hyperglycinemia:Possible involvement of alvcine in control of endogenous D-serine." Biochemical and Biophysical Research Communications. 231(3). 793-796 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuru A, et al.: "Abnormal expression of cell adhesion molecule L1 in migration disorder:A developmental immunohistochemical study." Clinical Neuropathology. 16(3). 122-126 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M.: "Development of Synaptic Transmission in Mental Retardation." National Center of Neurology and Psychiatry, 9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takashima S et al.: "Congenital Muscular Dystrophies." Elsevier Science B.V., 8 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M,et al.: "Tuberin loss from cerebral tissues-Reply." Ann Neurol. 47(2). 271-272 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M,et al.: "Tuberin immunohistochemistry in brain, kidneys and heart with or without tuberous sclerosis." Acta Neuropathol. 94(6). 532-538 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Clark GD,et al.: "Predominant localization of the LIS family of gene products to Cajal-Retzius cells and ventricular neuroepithelium in the developing human cortex." J Neuropathol Exp Neurol. 56(9). 1044-1052 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuru A,et al.: "Abnormal expression of cell adhesion molecule L1 in migration disorder : A developmental immunohistochemical study." Clin Neuropathol. 16(3). 122-126 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iwama H,et al.: "Depletion of cerebral D-serine in non-ketotic hyperglycinemia : Possible involvement of glycine in control of endogenous D-serine." Biochem Biophys Res Commun. 231(3). 793-796 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takashima S et al.: "Cytoarchitectonic alterations of the cerebral cortex in Fukuyama-type congenital muscular dystrophy and other cortical dysplasia syndrome." Fukuyama Y,Osawa M,Saito K (eds) Congenital Muscular Dystrophies.199-206 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M.: "Developmental expression of lissencephaly and tuberous sclerosis gene products." National Center of Neurology and Psychiatry (ed) Development of Synaptic Transmission in Mental Retardation.55-63 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mizuguchi M., et al.: "Tuberin loss from cerebral tissues-Reply." Annals of Neurology. 47(2). 271-272 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizuguchi M., et al.: "Tuberin immunohistochemistry in brain,kidneys and heart with or without tuberous sclerosis." Acta Neuropathologica. 94(5). 532-538 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Clark GD, et al.: "Predominant localization of the LIS family of geneproducts to Cajal-Retzius cells and ventricular neuroepithelium in the developing human cortex." Journal of Neuropathology and Experimental Neurology. 56(9). 1044-1052 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwama H, et al.: "Depletion of cerebral D-serine in non-ketotic hyperglycinemia:Possible involvement of alvcine in control of endogenous D-serine." Biochemical and Biophysical Research Communications. 231(3). 793-796 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuru A, et al.: "Abnormal expression of cell adhesion molecule L1 in migration disorder:A developmentalimmunohistochemical study" Clinical Neuropathology. 16(3). 122-126 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizuguchi M.: "Development of Synaptic Transmission in Mental Retardation." National Center of Neurology and Psychiatry, 9 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takashima S et al.: "Congenital Muscular Dystrophies." Elsevier Science B.V., 8 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizuguchi M,et al.: "Loss of tuberin from cerebral tissues with tuberous sclerosis and astrocytoma." Annals of Neurology. 40. 941-944 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Isumi H,et al.: "Expression of the LIS-1 gene product in brain anomalies with a migration disorder." Pediatric Neurology. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuru A,et al.: "Immunohistochemical expression of cell adhesion molecule L1 during development of the human brain." Early Human Development. 45. 93-101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Arai Y,et al.: "Excessive glutamate receptor 1 immunoreactivity in adult Down syndrome brains." Pediatric Neurology. 15. 203-206 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 水口雅: "中枢神経病変と結節性硬化症" 病理と臨床. 15. 100-104 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-03-31   Modified: 2016-04-21  

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