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Effect of stress and nutrition on brain functions: Mechanism-based risk evaluation of combined exposure

Research Project

Project/Area Number 11557028
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hygiene
Research InstitutionThe University of Tokyo

Principal Investigator

WATANABE Chiho  The University of Tokyo, Graduate School of Medicine, Assoc. Prof., 大学院・医学系研究科, 助教授 (70220902)

Co-Investigator(Kenkyū-buntansha) IMAI Hideki  National Institute for Environmental Studies, Endocrine Disruptors and Dioxins Research Project, Senior Research Scientist, 内分泌かく乱化学物質プロジェクト, 主任研究員 (00232596)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordscombined exposure / stress / Se deficiency / glucocorticoid / oxidative stress / behavioral functions / glutathione / neurotoxicity / 有機スズ / オープンフィールド行動 / 回転ふみ車運動 / 海馬 / 行動毒性 / 脳 / 免疫組織化学 / GFAP / ドパミン / 線条体
Research Abstract

One characteristic feature shared by most of the contemporary issues in the environmental health is that many causative agents are associated with a single health problem. In this study, attempts were made to develop an effective approach to evaluate the relative importance of each environmental agents in terms of human health risk. Brain dysfunctions were chosen as the target. As the models for the brain dysfunctions, hippocampal lesions induced by stresses and the striatum lesions induced by selenium (Se) deficiency. Moreover, the stress was combined with trimethyl tin (TMT), a chemical known to damage the hippocampus; on the other hand, the deficiency was combined with stress. As such interaction between a nutrient and a stress factor would be fully examined. In the hippocampal model, it was found that TMT-induced lesions were aggravated by adrenarectomy and alleviated by the administration of glucocorticoid, an observation contradict with the current belief. In the striatal model, it was shown for the first time that Se deficiency introduced after weaning is able to induce some behavioral anomaly. Although the openfield activity was reduced by the treatment with dexamethasone, there was no distinct interaction. In addition, a method was established to determine the extracellular concentrations of glutathione, a tripeptide responsible for the scavenge, in the striatum. This microdialysis technique revealed that hydrogen peroxide, an ROS generator, or desferal, a divalent iron chelator.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Imai H.et al.: "Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation〜"EXP.Neurol.. 171. 22-28 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsumi S. et al.: "Circulating corticosterone altars the rate of neuropathological and behavioral changes 〜"EXP.Neurol.. 173. 86-94 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 渡辺 知保: "セレン欠乏と脳機能"日本衛生学雑誌. 55. 581-589 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 渡辺 知保: "セレン欠乏と神経行動機能"Biomed res Trace Elements. 11. 331-332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 今井 秀樹: "ストレスと海馬-有機錫化合物投与による実験動物の〜"医学のあゆみ. 194. 286-287 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 渡辺 知保: "脳におけるセレン:特異的機能はあるのか?"Biomed res Trace Elements. 12. 197-206 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imai H. et al.: "Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the hippocampus"Experimental Neurology. vol.171. 22-28 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsutsumi S. et al.: "Circulating corticosterone alters the rate of neuropathological and behavioral changes induced by trimethyltin"Experimental Neurtology. vol.173. 86-94 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Watanabe C. et al.: "Selenium deficiency and brain functions (in Japanese)"Jpn J. Hygiene. vol.55. 581-589 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Watanabe C. et al.: "Selenium deficiency and, neurobehavioral functions"Biomedical Res on Trace Elem. vol.11. 331-332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imai H.: "Stress and hippocampus - an animal model of stress with trimethyltin administration"Igaku no Ayumi. vol.197. 286-287 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Watanabe C.: "Selenium in the brain : any specific functions?"Biomed Res on Trace Elem. vol.12. 197-206 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imai, et al.: "Type II glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in rhe at hippocampus"Experimental Neurology. 171. 22-28 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 今井 秀樹: "ストレスと海馬"医学のあゆみ. 197・4. 286-287 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsumi, et al.: "Circulating corticosterone alters the rate of neuropathological and behavioral"Experimental Neurology. 173. 86-94 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 渡辺 知保: "脳におけるセレン:特異的機能はあるのか?"Biomedical Research on Trace Elements. 12.3. 197-206 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imai H et al.: "Type I glucocorticoid receptors are involved in neuronal death and astrocyte activation induced by trimethyltin in the rat hippocampus."Exp.Neurol.. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 渡辺知保: "セレン欠乏と脳機能"日本衛生学雑誌. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] 今井秀樹: "ストレスと海馬-有機錫化合物投与による実験動物のストレスモデル"医学のあゆみ. 197・4(印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] 渡辺知保: "セレン欠乏と神経行動機能"Biomedical Research on Trace Elements. 11・4. 331-332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imai et al.: "Type(I)glucoconticod receptors are involved in neuronal death and astrocyte activation induced by trimethyltin"Exp.Neural.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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