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Functional Role of Fibroblast Growth Factors in the Central Nervous System

Research Project

Project/Area Number 05558095
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

SAITO Hiroshi  The University of Tokyo Professor, 薬学部, 教授 (00012625)

Co-Investigator(Kenkyū-buntansha) MATSUKI Norio  The University of Tokyo Associate Professor, 薬学部, 助教授 (70126168)
FURUKAWA Shoei  Gifu Pharmaceutical University Professor, 薬学部, 教授 (90159129)
KIMURA Hiroshi  Shiga University of Medical Science Professor, 分子神経生物学研究センター, 教授 (40079736)
NISHIKAWA Katsuzo  Kanazawa Medical University Professor, 医学部, 教授 (10029960)
OOMURA Yutaka  Nippon Zoki Pharmaceutical Co.Head Consultant, 生物活性科学研究所, 最高顧問 (30019517)
阿部 和穂  東京大学, 薬学部, 助手 (60202660)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1993: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsNeurotrophic Factor / Neurite Elongation / Neurite Branching / Memory / Learning / Regeneration / Neurotransmission / Long-term Potentiation / FGF / 神経再生、生存 / 遺伝子発現 / FGF受容体 / 線芽細胞成長因子 / 神経再生・生存 / 記憶・学習 / 脳
Research Abstract

We have found the following new results : 1) basic fibroblast growth factor (bFGF) promotes the survival of brain neurons both in vitro and in vivo, 2) bFGF increases the branching of cultured hippocampal neurons, 3) bFGF increases the expression of L-type calcium channels especially in the neurites, 4) bFGF augments the long-term potentiation (LTP) of the hippocampus both in vitro and in vivo, 5) bFGF improves the deteriorated learning and memory in mice and rats, 6) bFGF decreases spontaneous firing of cultured hippocampal neurons, 7) bFGF attenuates the depolarization-induced release of glutamate, 8) acidic FGF (aFGF) also promotes LTP,9) amino-terminal fragment of aFGF is important for biological effects, 10) aFGF improves memory and immunoreactivity of senescence accelerated mice, 11) nuclear localization of bFGF is detected using monoclonal antibody, 12) type-1 bFGF receptor is present in the cytoplasm as well as in the plasmamembrane, 13) type-1 bFGF receptors are concentrated especially in the neurons of hypothalamus, pars compacta of substantiae nigrae, locus coeruleus and raphe nuclei, 14) these neurons project the cortex, 15) localization and expression of aFGF are clearly different from those of nerve growth factor, 16) cultured neurons secrete aFGF.FGF would be a new type of drugs that improve brain function.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] A.Hamaguchi et al.: "Demonstration of fibroblast growth factor receptor-1 in human prostate by polymerase chain reaction and immunohistochemistry." Prostate. 27. 141-147 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sasaki et al.: "An amino-terminal fragment peptide of acidic fibroblast growth factor modulates synaptic transmission in rat hippocampal slices." Brain Res.Bull.38. 185-191 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Tooyama et al.: "Effect of acidic fibroblast growth factor on basal forebrain cholinergic neurons in senescence accelerated mice." Exp.Gerontol.(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Kaechi et al.: "4-Methylcatechl,an induceer of NGF synthesis,enhances peripheral nerve regeneratin across nerve gaps." J.Pharmacol.Exp.Ther.272. 1300-1304 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tanaka et al.: "Intracellular calcium oscillation in cultured rat hippocampal neurons : a model for glutamatergic neurotransmission." Japan.J.Pharmacol.70. 89-93 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] O.Ohta et al.: "Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas." Brit.J.Cancer.72. 824-831 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Koike et al.: "Effect of fibroblast growth factors on calcium currents in acutely isolated neuronal cells from rat ventromedial hypothalamus." Neurosci.Lett.150. 57-60 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Miyagawa et al.: "Branching enhancement by basic fibroblast growth factor in cut neurite of hippocampal neurons." Neurosci.Lett.153. 29-31 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Shitaka et al.: "The effect of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on the survival of septal neurons transplanted into the third ventricle in rats." Japan.J.Pharmacol.64. 27-33 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Aoyagi et al.: "Characterization of basic fibroblast growth factor-mediated acceleration of axonal branching in cultured rat hippocampal neurons." Brain Res.661. 117-126 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Aoyagi et al.: "Differential effects of microtubule inhibitors on axonal branching and elongation of cultured rat hippocampal neurons." Japan.J.Pharmacol.68. 223-226 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tanaka et al.: "Intracellular calcium oscillation in cultured rat hippocampal neurons : a model for glutamatergic neurotransmission." Japan.J.Pharmacol.70. 89-93 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tanaka et al.: "Basic fibroblast growth factor modulates synaptic transmission in cultured rat hippocampal neurons." Brain Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Noda et al.: "Attenuation of depolarization-induced release of glutamate by basic fibroblast growth factor." (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Oomura et al.: "Memory facilitation educed by food intake." Physiol.Behav.54. 493-498 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Matuso et al.: "Immunohistochemical localization of fibroblast growth factor receptor-1 in the rat brains." Neurosci.60. 48-66 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K Sasaki et al.: "Acidic fibroblast growth factor facilitates generation of long-term potentiation in rat hippocampus slices." Brain Res.Bull.33. 505-511 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sasaki et al.: "Effects of fibroblast growth factors and related peptides in food intake by rats." Physiol.Behav.56. 211-218 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sasaki et al.: "Action of acidic fibroblast growth factor fragments on food intake in rats." Obes.Res.3 (suppl.5). 6975-7065 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sasaki et al.: "An amino-terminal fragment peptide of acidic fibroblast growth factor modulates synaptic transmission in rat hippocampal slices." Brain Res.Bull.38. 185-191 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Oomura et al.: "Acidic fibroblast growth factor protects memory and immunoreactivity impairment in senescence accelerated mice." Neurobiol.3. 371-380 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sasaki et al.: "Effect of acidic fibroblast growth factor on neuronal activity of the parvocellular part in rat paraventricular nucleus." Neurobiol.3. 329-338 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Li et al.: "Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake." Exp.Neurol.137. 318-323 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Oomura et al.: "Protection against impairment of memory and immunoreactivity in senescence-accelerated mice by acidic fibroblast growth factor." Ann.NY Acad.Sci.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Minemura et al.: "In situ assay of basic fibroblast growth factor in cultured cells with a specific monoclonal antibody." Cell Struct.Funct.18. 313-323 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Nishikawa et al.: "Nuclear localization of specific function of basic fibroblast growth factor in tumor cells." Gann Monograph Cancer Res.42. 13-21 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Ohta et al.: "Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas." Br.J.Cancer. 72. 824-831 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Tooyama et al.: "Acidic and basic fibroblast growth factor-like immunoreactivity in the striatum and midbrain in Huntington's disease." Brain Res.610. 1-7 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Tooyama et al.: "Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease." Neurol. 43. 372-376 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Hara et al.: "Acidic fibroblast growth factor-like immunoreactivity in rat brain following cerebral infarction." Brain Res.664. 101-107 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kimura et al.: "Acidic FGF expression in the surroundings of senile plaques." Tohoku J.Exp.Med.174. 279-293 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Hamaguchi et al.: "Demonstration of fibroblast growth factor receptor-1 in human prostate by polymerase chain reaction and immunohistochemistry." Prostate. 27. 141-147 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Tooyama et al.: "Effect of acidic fibroblast growth factor on basal forebrain cholinergic neurons in senescence accelerated mice." Exp.Gerontol.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Nakajima et al.: "An improved solid-phase bioassay for neurotrophic factor." J.Neurochem.60. 267-273 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Awatsuji et al.: "Interleukin-2 as a trophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain." J.Neurosci.Res.35. 305-311 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nishio et al.: "Cellular localization of nerve growth factor-like immunoreactivity in adult brain : Quantitative and immunohistochemical study." Neurosci.60. 67-84 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Kechi et al.: "4-Methylcatechol, an inducer of NGF synthesis, enhances peripheral nerve regeneration across nerve gaps." J.Pharmacol.Exp.Ther.272. 1300-1304 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A. Hamaguchi et al.: "Demonstration of fibroblast growth factor receptor-1 in human prostate by polymerase chain reaction and immunohistochemistry." Prostate. 27. 141-147 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Sasaki et al.: "An amino-terminal fragment peptide of acidic fibroblast growth factor modulates synaptic transmission in rat hippocampal slices." Brain Res. Bull.38. 185-191 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I. Tooyama et al.: "Effect of acidic fibroblast growth factor on basal forebrain cholinergic neurons in senescence accelerated mice." Exp. Gerontol. (印刷中). (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Kaechi et al.: "4-Methylcatechl, an induceer of NGF synthesis, enhances peripheral nerve regeneratin across nerve gaps." J. Pharmacol. Exp. Ther.272. 1300-1304 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Tanaka et al.: "Intracellular calcium oscillation in cultured rat hippocampal neurons: a model for glutamatergic neurotransmission." Japan. J. Pharmacol.70. 89-93 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] O. Ohta et al.: "Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas." Brit. J. Cancer.72. 824-831 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Shitaka ら: "The effect of basic fibroblast growth factor and nerve groathfactor on the survival of septal neurons transplauted into the third ventvicle" Japan J.Pharmacol.64. 27-33 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Nishikawa ら: "Nuclear localization and specific fuuction of basic fibroblast growth factor in tumor cells." Gann Monograph Cancer Res.42. 13-21 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Aoyagi ら: "Characterization of basic fibroblast growth factor-mediated acceleration of axonal branching in cultured rat hippocampel neurons" Brain Res.661. 117-126 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Matsuo ら: "Imunohistochemical localization of an epitope corresponding to FGF receptor-I." Neuroscience. 60. 49-66 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] I.Tooyama ら: "Retention of basic fibrablast immunoreactivity in dopaminergic neurons of the substantia nigra during normal aging in humans." Brain Res.656. 165-168 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Nishio ら: "Cellular localization of nerve growth factor-liki immunoreuctivity inadult brain" Brain Res.641. 350-352 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古川昭栄: "ニュートロフィンの生理機能とアルツハイマー病" 学会出版センター, 124 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Oomuraら: "Memory facilitation educed by food intake." Physiol.Behav.54. 493-498 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] I.Tooyamaら: "Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease." Neurology. 43. 372-376 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] O.Amanoら: "Immunohistochemical localization of basic fibroblast growth factor in the rat pituitary gland." Arch.Histol.Cytol.56. 269-276 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Awatsujiら: "Interleukin-2 as a trophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain." J.Neurosci.Res.35. 305-311 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Miyagawaら: "Branching enhancement by basic fibroblast growth factor in cut neurite of hippocampal neurons." Neurosci.Lett.153. 29-31 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Koikeら: "Effect of fibroblast growth factors on calcium currents in acutely isolated neuronal cells from rat ventromedial hypothalamus." Neurosci.Lett.150. 57-60 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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