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On the mechanism of cerebellar foliation and its abnormal development

Research Project

Project/Area Number 09680741
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionNagoya University

Principal Investigator

INOUYE Minoru  Nagoya Univ., Res. Inst. Environ. Med., Associate Professor, 環境医学研究所, 助教授 (20090425)

Co-Investigator(Kenkyū-buntansha) TAKAGISHI Yoshiko  Nagoya Univ., Res. Inst. Environ. Med., Research Associate, 環境医学研究所, 助手 (50024659)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsCerebellum / extracellular matrix / foliation / prenatal exposure / Purkinje cell / radiation / rat / Reelin / X線 / 外顆粒細胞 / アポトーシス / 発生 / 神経細胞遊走 / バーグマン細胞
Research Abstract

Prenatal X-irradiation of rats during the late gestation period induces ectopic Purkinje cells in abnormally foliated cerebellum. To examine mechanisms of abnormal migration of Purkinje cells by X-radiation, pregnant rats were exposed to 2.5 Gy X-radiation on gestation day 21, and the cerebellum of progeny was examined using immunohistochemistry for identification of Purkinje and Bergmann cells. Six hours after exposure, extensive cell death was observed in the external granular layer (EGL). By postnatal day (P) 9, while Purkinje cells with well developed dendrites were aligned underneath the EGL in the control cerebellum, Purkinje cells with shorter and abnormally oriented dendrites failed to align and remained in the ectopic location mainly in the internal granular layer (IGL), and abnormal folia developed in the irradiated rats. Expression of cell adhesion molecules, i.e., neural cell adhesion molecule (NCAM), fibronectin, tenascin and Reelin, was examined by immunochemistry. Among them the expression of Reelin was affected most prominently. Reelin expression strikingly decreased in the premigratory zone of EGL and IGL in the irradiated cerebellum on P1, and the decrease continued until P9. Northern blot analysis also revealed significant decrease in Reelin mRNA by irradiation from P0, being almost one third of level in controls. The decrease continued up to P9. Expressions of other cell adhesion molecules examined were not affected following exposure and around the Purkinje cells. The results demonstrated that X-radiation caused disruption of EGL and reduced secretion of Reelin. Since Reelin has been shown to play important roles in the migration of neural cells, it is suggested that the decrease in Reelin is an important factor in the disturbed migration of Purkinje cells. The derangement of Purkinje cells may result in the abnormal foliation of the cerebellum by X-irradiation.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Darmanto, W., Inouye, M. ら: "Derangement of Purkinje cells in the rat cerebellum following prenatal exposure to X-irradiation : Decreased Reelin level is a possible cause"Journal of Neuropathology and Expermental Neurology. 59・(3)(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Darmanto, W., Inouye, M. et al.: "Derangement of Purkinje cells in the rat cerebellum following prenatal exposure to X-irradiation : Decreased Reelin level is a possible cause"Journal of Neuropathology and Experimental Neurology. 2000. ((in press))

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Darmanto,W.,Inouye,M.ら: "Derangement of Purkinje cells in the rat cerebellum following prenatal exposure to X-irradiation: Decreased Reelin level is a possible cause."Journal of Neuropathology and Experimental Neurology. 59・(3)(印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Darmanto W, Hayasaka S, Takagishi Y, Aolad HM, Inouye M.: "Sensitivity difference between anterior and posterior lobes of rat cerebellum to prenatal exposure to 2.5 Gy X-irradiation : a histological study" Environmental Medicine. 41,2. 93-96 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aolad HM, Hayasaka S, Darmanto W, Koyasu K, Oda S, Inouye M.: "Strain difference in the folial pattern of the cerebellum of house musk shrew,Suncus murinus" Environmental medicine. 41,2. 97-100 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Darmanto W, Inouye M, Hayasaka S, Takagishi Y, Aolad HM, Murata Y.: "Dose response relationship of disturbed migration of Purkinje cells in the cerebellum due to X-irradiation" Environmental Medicine. 42,1. 46-50 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Darmanto, W., Takagishi, Y, Inouye, M.et al.: "Sensitivity difference between anterior and posterior lobes of rat cerebellum to prenatal exposure to 2.5 Gy X-irradiation: a histological study" Environmental Medicine. 41巻・2号. 93-96 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aolad, H.M., Darmanto, W.,Inouye, M.et al.: "Strain difference in the folial pattern of the cerebellum of house musk shrew, Suncus murinus." Environmental Medicine. 41巻・2号. 97-100 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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