Optimizing neurotrophic factor combinations for neurite outgrowth
Optimizing neurotrophic factor combinations for neurite outgrowth
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DOI：
10.1088/1741-2560/3/2/011
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Schmidt, C. E.
中科院分区：
文献类型：
--
作者：
Deister, C.;Schmidt, C. E.
大多数神经营养因子是三个家族之一的成员：神经营养因子，神经胶质细胞系衍生的神经营养因子家族配体（GFLs）和神经生成细胞因子。每个家族激活不同但重叠的细胞通路。一些研究表明，来自不同家族的神经营养因子之间存在加法或协同作用，尽管通常只研究了一种单一的组合。由于神经营养因子之间可能存在相互作用，因此混合物中某一因子的最佳浓度可能不同于单独使用时的最佳浓度。此外，来自三个家族的神经营养因子组合对神经突延伸的影响尚不清楚。本研究探讨了神经营养因子神经生长因子（NGF）、GFL胶质细胞系衍生神经营养因子（GDNF）和神经生成细胞因子睫状神经营养因子（CNTF）几种组合对幼鼠背根神经节（DRG）外植体神经突生长的影响。50 ng ml(-1) NGF和10 ng ml(-1) GDNF和CNTF的组合诱导最高水平的神经突生长，比未处理的DRGs增加752 +/- 53%，最长神经突长度增加到2031 +/- 97 μ m，而未处理的DRGs为916 +/- 64 μ m。三种因子组合施用的最佳浓度与单独施用时各因子的最佳浓度相对应。这些结果表明，与以前的导管设计相比，神经营养因子、GFLs和神经生成细胞因子的组合在更高浓度下的控制释放将增强未来神经修复治疗的效果。
Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml(-1) NGF and 10 ng ml(-1) of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 +/- 53% increase over untreated DRGs and increased the longest neurite length to 2031 +/- 97 mu m, compared to 916 +/- 64 mu m for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.