Global expression of NGF promotes sympathetic axonal growth in CNS white matter but does not alter its parallel orientation.
Global expression of NGF promotes sympathetic axonal growth in CNS white matter but does not alter its parallel orientation.
复制标题
NGF 的整体表达促进中枢神经系统白质中交感神经轴突的生长，但不会改变其平行方向。
DOI：
10.1016/j.expneurol.2006.07.026
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发表时间：
2007
影响因子：
5.3
通讯作者：
Crutcher,KeithA
中科院分区：
文献类型：
--
作者：
Pettigrew,DavidB;Li,Ya-Qin;Kuntz4th,Charles;Crutcher,KeithA
中枢神经系统白质损伤后，轴突再生通常是有限的。神经营养因子的输注成功地通过损伤的白质促进了再生生长，但这种生长通常无法延伸到输液部位以外。这些观察结果与这些因子对轴突生长的趋化作用是一致的，并支持了神经营养素诱导的轴突再生需要使用梯度，即沿着靶纤维束逐渐增加神经营养素水平的流行观点。为了研究神经营养因子的整体过表达对促进和/或改变白质内再生轴突生长方向的潜在作用，我们在神经胶质纤维酸性蛋白启动子的控制下，将神经生长因子(NGF)反应神经元移植到在整个中枢神经系统中高表达NGF的转基因小鼠的胼胝体中。一周后，移植物周围受损白质内胶质纤维酸性蛋白和硫酸软骨素蛋白多糖免疫反应增强。转基因小鼠脑内NGF水平明显高于非转基因小鼠，损伤部位NGF水平进一步高于非转基因小鼠的同型区域。尽管移植到非转基因小鼠体内的神经元只有很少的突起，但转基因小鼠在距星形胶质细胞瘢痕(NGF表达最多的部位)1.5 mm处的胼胝体内发生了广泛的平行轴突再生。这些结果表明，神经营养因子的全球过度表达并没有超越限制再生生长为平行方向的限制，并表明这些因素不需要以正梯度的形式出现，以促进白质内的轴突再生。
Axonal regeneration is normally limited after injuries to CNS white matter. Infusion of neurotrophins has been successful in promoting regenerative growth through injured white matter but this growth generally fails to extend beyond the infusion site. These observations are consistent with a chemotropic effect of these factors on axonal growth and support the prevailing view that neurotrophin-induced axonal regeneration requires the use of gradients, i.e., gradually increasing neurotrophin levels along the target fiber tract. To examine the potential of global overexpression of neurotrophins to promote, and/or modify the orientation of, regenerative axonal growth within white matter, we grafted nerve growth factor (NGF) responsive neurons into the corpus callosum of transgenic mice overexpressing NGF throughout the CNS under control of the promoter for glial fibrillary acidic protein. One week later, glial fibrillary acidic protein and chondroitin sulfate proteoglycan immunoreactivity increased within injured white matter around the grafts. NGF levels were significantly higher in the brains of transgenic compared with non-transgenic mice and further elevated within injury sites compared with the homotypic region of the non-injured side. Although there was minimal outgrowth from neurons grafted into non-transgenic mice, extensive parallel axonal regeneration had occurred within the corpus callosum up to 1.5 mm beyond the astrogliotic scar (the site of maximum NGF expression) in transgenic mice. These results demonstrate that global overexpression of neurotrophins does not override the constraints limiting regenerative growth to parallel orientations and suggest that such factors need not be presented as positive gradients to promote axonal regeneration within white matter.