Functional Role of Fibroblast Growth Factors in the Central Nervous System

成纤维细胞生长因子在中枢神经系统中的功能作用

• 批准号: 05558095
• 负责人: SAITO Hiroshi
• 金额: $ 8.64万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05558095/
• 关键词: Neurotrophic 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

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.

我们发现了以下新结果：1）基本成纤维细胞生长因子（BFGF）促进体外和体内脑神经元的存活率，2）BFGF增加了培养的海马神经元的分支，3）BFGF增加了L-的表达。类型的钙通道特别是在神经突中，4）BFGF在体外和体内增强了Hippocampus的长期增强（LTP），5）BFGF改善了小鼠和大鼠的衰减学习和记忆力，6）BFGF减少自发性解散在培养的海马神经元中，7）BFGF减弱了去极化诱导的谷氨酸释放，8）酸性FGF（AFGF）也促进了AFGF的LTP，9）AFGF的氨基末端碎片对生物学作用至关重衰老加速小鼠，11）使用单克隆抗体检测到BFGF的核定位，12）1型BFGF受体中存在于细胞质中以及浆膜中，13）1型BFGF受体被浓缩，质体nigrae，coeruleus和raphe nuclei的pars compacta，14）这些神经元项目的皮质，15）AFGF的定位和表达明显不同于神经生长因子的皮质，16）培养的神经元分泌的AFGF.FGF.FGF将是新的。改善大脑功能的药物类型。

项目成果

T.Ohta et al.: "Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas." Br.J.Cancer. 72. 824-831 (1995)

T.Ohta 等人：“碱性成纤维细胞生长因子及其受体在人胰腺癌中的表达”。

Y.Hara et al.: "Acidic fibroblast growth factor-like immunoreactivity in rat brain following cerebral infarction." Brain Res.664. 101-107 (1994)

Y.Hara 等人：“脑梗塞后大鼠脑中的酸性成纤维细胞生长因子样免疫反应性。”

K.Noda et al.: "Attenuation of depolarization-induced release of glutamate by basic fibroblast growth factor." (submitted).

K.Noda 等人：“碱性成纤维细胞生长因子减弱去极化诱导的谷氨酸释放。”

T.Tanaka et al.: "Basic fibroblast growth factor modulates synaptic transmission in cultured rat hippocampal neurons." Brain Res.(in press).

T.Tanaka 等人：“碱性成纤维细胞生长因子调节培养的大鼠海马神经元的突触传递。”

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)

A.Hamaguchi 等人：“通过聚合酶链反应和免疫组织化学演示人前列腺中的成纤维细胞生长因子受体 1。”