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Evaluation of the mechanism of membrane transport of metal ions in the central nervous system

Research Project

Project/Area Number 08457111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionHokkaido University

Principal Investigator

SAITO Takeshi  Hokkaido University School of Medicine, Associate Professor, 医学部, 助教授 (40153811)

Co-Investigator(Kenkyū-buntansha) HOSOKAWA Toshiyuki  Center for Reseach and Development in Higher Education, Hokkaido University, Ass, 助教授 (00157025)
SAITO Kazuo  Hokkaido University School of Medicine, Professor, 医学部, 教授 (80000917)
高倉 昌之  北海道大学, 医学部, 助手 (90241314)
神山 昭男  北海道大学, 医学部, 助教授 (90215202)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsTrace elements / Mechanism of transport / Brain / Aging, / Neurological dysfunction
Research Abstract

In the present study, we intended to evaluate the mechanism of membrane transport of metal ions in the central nervous system and its relation to the neurotransmission. Results obtained in the present investigations are as follows ;
1.We determined concentrations of trace elements and neurotransmitters (norepinephrine (NE) , dopamine (DA) ) and its metabolites in the brain of LEC rat ; an animal model of Wilson disease. NE depression as well as accumulation of DA in the cerebral cotex of the LEC rat occurred at a young age. These alterrations of the catecholamine metabolism at a young age may be due to the depression of DBH activity induced by Cu deficiency in this region. Our results suggest the hypothesis that neurochemical changes induced by brain Cu deficiency in the early stage of Wilson disease may be involved in the neurological disturbances in patients with this disease before excessive Cu accumulation in the brain.
2.Distribution of ATP7B,the copper-transporting protein responsible for Wilson disease, was determined in various organs of the LEA rat. ATP7B was detected in several neuronal cell groups such as pyramidal cells of CA1 to CA4 and granular cells of the dentate gyrus in the brain and the renal cortex of the kidney. These results suggest that ATP7B plays an important role in the regulation of Cu homeostasis and biosynthesis of holo-Cu-binding proteins in tissues.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 齋藤 健: "Distriburion of the copper transporting P-type ATPase (ATP7B) in the kidney ,brain and liver of the rat." J.Inorg.Biochem.67. 58 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 齋藤 健: "銅の膜輸送蛋白P-type ATPase(ATP7B)のラット脳組織内分布" Biomedical Reseach on Trace Elements. 8. 329-330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 岡部 雅史: "Histochemical localization of superoxide dismutase in rat brain." Free Radical Biology and Medicine. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 中川 典子: "Changes in trace element concentrations in eight brain regions of the senecence accelerated mouse (SAM) by aging." J.Inorg.Biochem.67. 47 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 齋藤 健: "Neurochemical and histochemical evidence for an abnormal catecholamine metabolism in the cerebral cortex of the Long-Evans Cinnamon rat before excessive copper accumulation in the brain." Neurosci.Lett.216. 195-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] SAITO Takeshi: "Distribution of the copper transporting P-type ATPase (ATP7B) in the kidney, brain and liver of the rat." J.Inorg.Biochem.67. 58 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] SAITO Takeshi: "Distribution of copper transporting P-type ATPase (ATP7B) in rat brain" Biomedical Reseach on Trace Elements. 8. 329-330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] OKABE Masashi: "Histochemical localization of superoxide dismutase in rat brain." Free Radical Biology and Medicine.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] NAKAGAWA Noriko: "Changes in trace element concentrations in eight brain regions of the senecence accelerated mouse (SAM) by aging." J.Inorg.Biochem.67. 47 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] SAITO Takeshi: "Neurochemical and histochemical evidence for an abnormal catecholamine metabolism in the cerebral cortex of the Long-Evans Cinnamon rat before excessive copper accumulation in the brain." Neurosci.Lett.216. 195-198 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 齋藤 健: "Distribution of the copper transporting P-type ATPase(ATP7B)in the kidney,brain and liver of the rat." J.Inorg.Biochem.67. 58- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 齋藤 健: "銅の膜輸送蛋白P-type ATPase(ATP7B)のラット脳組織内分布" Biomedical Reseach on Trace Elements. 8. 329-330 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 岡部 雅史: "Histochemical localization of superoxide dismutase in rat brain." Free Radical Biology and Medicine. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中川 典子: "Changes in trace element concentrations in eight brain regions of the senecence accelerated mouse(SAM)by aging." J.Inorg.Biochem.67. 47- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 斎藤 健: "Neurochemical and histochemical evidence for an abnormal catecholamine metabolism in the cerebral cortex of the Long-Evans Cinnamon rat before excessive copper accumulation in the brain." Neurosci. Lett.216. 195-198 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 斎藤 健: "Simultaneous multi-determination of brain trace element concentrations by inductively coupled plasma mass spectrometry." Tohoku J. Exp. Med.178. 11-16 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 伊藤俊弘: "Endogenous zinc release in the hippocampus of the anesthetized rat brain using microdialysis." Trace Elements and Electrolytes. 13. 196-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 斎藤 健: "微量元素と加齡." 総合臨床. 45. 2439-2440 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 斎藤 健: "必須微量元素の生体内動態-吸収、輸送、貯蔵、排泄のメカニズム-" 日本臨床. 54. 12-16 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 斎藤 健: "生体内微量元素の動態とその生理的機能-情報伝達機構における微量元素の役割-" 日本衛生学雑誌. 51. 103-106 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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