The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia [published erratum appears in J Neurosci 1992 Mar;12(3):685]
The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia [published erratum appears in J Neurosci 1992 Mar;12(3):685]
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DOI：
10.1523/jneurosci.11-10-03070.1991
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发表时间：
1991-10
期刊：
影响因子：
--
通讯作者：
Jiirgen Engele;M. Bohn
中科院分区：
文献类型：
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作者：
Jiirgen Engele;M. Bohn
神经营养支持通常被认为是生长因子对发育中的神经元的直接作用。然而，越来越多的证据表明，生长因子可以通过胶质细胞介导的过程间接影响神经元的发育。为探讨胶质细胞在多巴胺能神经元神经营养作用中的可能作用，筛选了4种纯化的生长因子对多巴胺能神经元的存活、分化和中脑胶质细胞增殖的双重作用。分离的胚胎14.5天的大鼠中脑在无血清的低细胞密度下生长，在这种条件下胶质细胞生长和神经元存活都不是最佳的。用酸性成纤维细胞生长因子或碱性成纤维细胞生长因子处理8d后，酪氨酸羟化酶免疫反应神经元存活数增加90-110%，且呈剂量依赖关系。这些因素的影响不是相加的。高亲和力的多巴胺摄取可被bFGF增加，但不能被aFGF所增加。碱性成纤维细胞生长因子和碱性成纤维细胞生长因子均不影响TH-IR神经突起的长度。~3H-胸腺嘧啶核苷放射自显影结合胶质纤维酸性蛋白(GFAP)免疫细胞化学染色显示，两种生长因子均可诱导中脑星形胶质细胞增殖。而血小板衍生生长因子(PDGF)和白介素1对多巴胺能神经元的存活、分化和中脑星形胶质细胞的增殖均无影响。抑制神经胶质细胞的增殖可阻断aFGF或bFGF对多巴胺能神经元的神经营养作用。此外，在没有神经元的情况下，来自中脑胶质细胞培养的条件培养液也含有神经营养活性。
Neurotrophic support is generally believed to result from a direct action of growth factors on developing neurons. However, there is increasing evidence that growth factors can indirectly affect neuronal development by glial-mediated processes. To investigate a possible role of glia in mediating neurotrophic effects on dopaminergic neurons, four purified growth factors were screened for dual effects on the survival and differentiation of dopaminergic neurons and on the proliferation of mesencephalic glial cells in vitro. Dissociated embryonic day 14.5 rat mesencephalon was grown at low cell density without serum, conditions under which both glial growth and neuronal survival are not optimal. Treatment of these cultures with acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) increased the number of surviving tyrosine hydroxylase-immunoreactive (TH-IR) neurons by 90- 110% [corrected] at 8 d in vitro in a dose-dependent manner. The effects of these factors were not additive. High-affinity dopamine uptake was increased by bFGF, but not by aFGF. Length of TH-IR neurites was not affected by either aFGF or bFGF. Both growth factors induced proliferation of mesencephalic astrocytes as demonstrated by autoradiographic labeling with 3H-thymidine combined with immunocytochemistry for glial fibrillary acidic protein (GFAP). In contrast, platelet-derived growth factor (PDGF) and interleukin-1 had no effect on the survival or differentiation of dopaminergic neurons or the proliferation of mesencephalic astrocytes. Inhibition of glial proliferation abolished the neurotrophic effects exerted by aFGF or bFGF on dopaminergic neurons. Moreover, conditioned medium derived from mesencephalic glial cultures replated in the virtual absence of neurons also contained neurotrophic activity.(ABSTRACT TRUNCATED AT 250 WORDS)