Walicke P, Cowan W M, Ueno N, Baird A, Guillemin R
Proc Natl Acad Sci U S A. 1986 May;83(9):3012-6. doi: 10.1073/pnas.83.9.3012.
Basic fibroblast growth factor (FGF) has been found to increase neuronal survival and neurite extension in a highly purified population of fetal rat hippocampal neurons under well-defined serum-free cell culture conditions. In the presence of FGF, neuronal survival after 7 days in culture on a simple plastic substrate is increased 4-fold, to 54% of the initial population. Survival is increased 2-fold to 40% on polyornithine-laminin. When FGF was bound to plastic or heparin substrates, neurite outgrowth was significantly increased to lengths comparable to those seen with laminin; however, FGF produced no further increase in neurite outgrowth on laminin. Half-maximal survival was observed at FGF concentrations of about 15 pg/ml (1 pM); half-maximal process outgrowth occurred at about 375 pg/ml (20 pM). The responsive cells were identified as neurons by their labeling with tetanus toxin and by antibodies to neurofilaments and to the neuron-specific enolase. Astrocytes, identified by the presence of glial fibrillary acidic protein, constituted about 10% of cells present at 1 week both in the presence and in the absence of FGF. These results strongly suggest that, in addition to its known mitogenic effects on nonneuronal cells, FGF possesses neurotrophic activity for hippocampal neurons.
在明确的无血清细胞培养条件下，已发现碱性成纤维细胞生长因子（FGF）可提高高度纯化的胎鼠海马神经元群体的神经元存活率并促进神经突延伸。在FGF存在的情况下，在简单塑料底物上培养7天后，神经元存活率提高了4倍，达到初始群体的54%。在聚鸟氨酸-层粘连蛋白上，存活率提高了2倍，达到40%。当FGF与塑料或肝素底物结合时，神经突生长显著增加，达到与层粘连蛋白相当的长度；然而，FGF在层粘连蛋白上并未进一步增加神经突生长。在FGF浓度约为15 pg/ml（1 pM）时观察到半数最大存活率；半数最大突起生长发生在约375 pg/ml（20 pM）时。通过用破伤风毒素标记以及使用抗神经丝和抗神经元特异性烯醇化酶的抗体，将反应性细胞鉴定为神经元。通过胶质纤维酸性蛋白的存在鉴定的星形胶质细胞，在有和没有FGF的情况下，在1周时均占细胞总数的约10%。这些结果强烈表明，除了其对非神经元细胞已知的促有丝分裂作用外，FGF对海马神经元具有神经营养活性。
