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免疫抑制剤とその誘導体による脊髄損傷修復の基礎的研究

Research Project

Project/Area Number 11878158
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

古川 昭栄  岐阜薬科大学, 薬学部, 教授 (90159129)

Co-Investigator(Kenkyū-buntansha) 新田 淳美  岐阜薬科大学, 薬学部, 助手 (20275093)
野元 裕  岐阜薬科大学, 薬学部, 助教授 (80164747)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsイムノフィリン / イムノフィリンリガンド / 神経栄養因子 / 神経再生 / 神経疾患 / 線条体 / 脊髄損傷 / サイクロスポリンA / グリア細胞株由来神経栄養因子 / ラット / 遺伝子導入 / 酵素免疫測定法 / 脳由来神経栄養因子 / 免疫抑制剤 / ドパミン作動性神経系 / タクロリムス / マウス
Research Abstract

これまでの研究により、免疫抑制剤を含むイムノフィリンリガンドが神経栄養因子の産生を促進する活性を持つことが明らかとなった。これまで知られていたイムノフィリンリガンドによる神経保護作用の少なくとも一部はこの神経栄養因子産生促進活性に起因すると推定された。しかし神経保護作用を期待するとき免疫抑制作用は生体に不利益をもたらす恐れがある。昨年度は免疫抑制作用をもたないイムノフィリンリガンドリガンドとしてLeu-Ileジペプチドを見出した。本年度は、生体内でのLeu-Ileジペプチド機能について検討した。PBSに溶解したLeu-Ileをマウス脳室内または腹腔内に1日1回、10日間投与し、最終投与から24時間後に線条体の脳由来神経栄養因子(BDNF)およびグリア細胞株由来神経栄養因子(GDNF)含量を測定した。その結果、Leu-Ileの脳室内投与、腹腔内投与いずれの場合も明瞭なBDNF、GDNF含量の増加を認めた。腹腔内投与の場合、Leu-Ileは血中では不安定であり、脳・血液関門通過性にも問題があると推定されたが、脳室内投与に遜色のない効果を引き出した。すなわちLue-Ileジペプチドは免疫抑制作用をもたず、神経細胞保護効果をもつイムノフィリンリガンドとして有望である。これらの免疫抑制作用をもたないイムノフィリンリガンドをリード化合物してさらに強力な活性物質が創製できれば、脊髄損傷をはじめとする中枢神経疾患の治療薬の開発につながるものと期待される。

Report

(3 results)
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Ohmiya et al.: "Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex"Journal of Neuroscience Research. 65. 228-235 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sometani et al.: "Transforming growth factor-beta 1 enhances expression of brain-derived neurotrophic factor and its receptor, TrkB, in neurons cultured from rat cerebral cortex"Journal of Neuroscience Research. 66. 369-376 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawagishi et al.: "Purification and characterization of two lectins from toxic moray, Gymnothrax javanicus.-2442"Bioscience, Biotechnology and Biochemistry. 65. 2437-2442 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohmiya et al.: "Brain-derived neurotrophic factor alters cell migration of particular progenitor cells in the developing mouse cerebral cortex"Neuroscience Letters. 377. 21-24 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 古川昭栄: "神経栄養因子の産生調節機構 -Ca^<2+>とcAMPシグナルのクロストーク-"組織培養工学. 27. 500-505 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuta et al.,: "Difference in toxicity of amyloid b peptide with aging in relatuin to nerve growth factor contenr in rat brain"Journal of Neuronal Transsmission. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikemoto et al.,: "Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus"Neuroscience Letters. 285. 99-102 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 新田淳美と古川昭栄: "神経栄養因子(特集;アルツハイマー病と異常蛋白沈着による痴呆症をめぐる最近の話題)"Pharma Medica. 18. 87-93 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawakami et al.,: "Increase in neurotrophin-3 expression followed by Purkinje cell degeneration in the adult rat cere"Journal of Neuroscience Research. 62. 668-674 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukumitsu et al.,: "Aberrant expression of neurotrophic factors in the ventricular progenitor cells of infant congenitally hydrocephalic rats."Childs Nervous System. 16. 516-521 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nomoto et al.,: "Balance of two secretion pathway of nerve growth factor in PC12 cells changed during the progression of their differentiation, with a decrease in in constitutive secretion in more differentiated cells"Journal of Neuroscience Research. 59. 634-642 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Nitta et al.: "Endogenous neurotrophin-3 is retrogradely transported in the rat sciatic nerve"Neuroscience. 88. 679-685 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Nitta et al.: "Brain-derived neurotrophic factor prevents neuronal cell death induced by corticosterone"J.Neurosci.Res.. 57. 227-235 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Nitta et al.: "4-methylcatechol increases brain-derived neurotrophic factor content and mRNA expression in cultured brain cells and in rat brain in vivo"J.Pharmacol.Exp.Ther.. 291. 1276-1283 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Fukumitsu et al.: "Induction of a physiologically active brain-derived neurotrophic factor in the Infant rat brain by peripheral administration of 4-methylcatechol"Neurosci.Lett.. 274. 115-118 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Mizuma et al.: "Microsphere embolism-induced elevation of nerve growth factor level and appearance of nerve growth factor immunoreactivity in activated T-lymphocytes in the rat brain"J.Neurosci.Res.. 55. 749-761 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Furukawa et al.: "神経栄養因子による神経細胞の保護"最新医学. 54. 1730-1736 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Nitta and S.Furukawa: "痴呆症の治療と予防 神経栄養因子"Pharma Medica. 18. 87-93 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Furukawa and S.Furukawa: "遺伝子治療ハンドブック"エヌ・ティー・エヌ. 1061 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Furukawa: "Glia細胞"クバプロ. 359 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Furukawa and A.Nitta: "Keio University symposia for life science and medicine,Vol.2 Neural Development"Springer. 544 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Nitta et al.: "Keio University symposia for life science and medicine,Vol.2 Neural Development"Springer. 544 (1999)

    • Related Report
      1999 Annual Research Report

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

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