Woodward W R, Nishi R, Meshul C K, Williams T E, Coulombe M, Eckenstein F P
Department of Neurology, Oregon Health Sciences University, Portland 97201.
J Neurosci. 1992 Jan;12(1):142-52. doi: 10.1523/JNEUROSCI.12-01-00142.1992.
Fibroblast growth factors (FGFs) are known to stimulate mitogenesis in a variety of non-neuronal cell types and to support the survival in vitro of many neuronal cell types. The physiological role of FGFs in the CNS is currently not known. The present study determined the distribution in the rat CNS of a prominent member of the FGF family, basic FGF (bFGF). Immunohistochemical analysis showed that bFGF immunoreactivity was found predominantly in astrocytes throughout all regions of the CNS. In contrast, only a few neuronal populations were found to contain bFGF immunoreactivity, most prominent among them, neurons in the CA2 area of the hippocampus. This predominant localization of bFGF to astrocytes was confirmed by two other observations: (1) highly enriched cultures of astrocytes contained bFGF immunoreactivity and bioactivity, whereas highly enriched cultures of cerebral cortical neurons contained no detectable bFGF, and (2) neonatal rat cerebral cortex, which contains only a few differentiated astrocytes, also contained no detectable bFGF immunoreactivity and only low amounts of bFGF bioactivity. Immunocytochemical analysis also suggested that bFGF immunoreactivity was present in the nucleus as well as the cytoplasm of astrocytes and CA2 neurons. This nuclear localization was confirmed by EM analysis of the intracellular distribution of the immunoperoxidase reaction product. In addition, preparations of both nuclear and soluble fractions of brain extracts contained bFGF immunoreactivity and bioactivity. These data suggest that bFGF might be involved in mediating astrocytic influences on the late postnatal maturation and plasticity in the CNS, and that the nuclear localization of bFGF within astrocytes may play an important role in the differentiation of these cells. In addition, bFGF may play a similar role in a few specific neuronal populations, such as CA2 hippocampal neurons.
成纤维细胞生长因子（FGFs）已知可刺激多种非神经元细胞类型的有丝分裂，并支持多种神经元细胞类型在体外的存活。FGFs在中枢神经系统中的生理作用目前尚不清楚。本研究确定了FGF家族的一个重要成员——碱性成纤维细胞生长因子（bFGF）在大鼠中枢神经系统中的分布。免疫组织化学分析表明，bFGF免疫反应性主要在中枢神经系统所有区域的星形胶质细胞中发现。相比之下，仅发现少数神经元群体含有bFGF免疫反应性，其中最显著的是海马CA2区的神经元。另外两个观察结果证实了bFGF在星形胶质细胞中的这种主要定位：（1）高度富集的星形胶质细胞培养物含有bFGF免疫反应性和生物活性，而高度富集的大脑皮质神经元培养物未检测到bFGF，以及（2）仅含有少量分化星形胶质细胞的新生大鼠大脑皮质也未检测到bFGF免疫反应性，且仅含有少量bFGF生物活性。免疫细胞化学分析还表明，bFGF免疫反应性存在于星形胶质细胞和CA2神经元的细胞核以及细胞质中。这种核定位通过对免疫过氧化物酶反应产物细胞内分布的电子显微镜分析得到证实。此外，脑提取物的核组分和可溶性组分制剂均含有bFGF免疫反应性和生物活性。这些数据表明，bFGF可能参与介导星形胶质细胞对中枢神经系统产后晚期成熟和可塑性的影响，并且bFGF在星形胶质细胞内的核定位可能在这些细胞的分化中起重要作用。此外，bFGF可能在少数特定的神经元群体中发挥类似作用，如海马CA2神经元。
