Nerve growth factor-mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor
Nerve growth factor-mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor
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DOI：
10.1002/cne.20537
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发表时间：
2005-06-13
影响因子：
2.5
通讯作者：
Kawaja, MD
中科院分区：
文献类型：
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作者：
Hannila, SS;Kawaja, MD
本研究使用以下基因型小鼠：野生型、p75神经营养因子受体（p75NTR）外显子III缺失突变、NGF转基因和NGF转基因p75NTR外显子III缺失突变（NGF/p75(-/-)），检测了神经生长因子（NGF）应答性背根神经节（DRG）中枢突的生长能力。在野生型和p75NTR外显子III零突变小鼠中，根切断法后3天和28天，小鼠背角的降钙素基因相关肽（CGRP）免疫反应性显著降低。NGF转基因小鼠和NGF/p75（-/-）小鼠在根断后3天也表现出CGRP免疫反应性降低，但在术后28天，这些小鼠受伤的背角中观察到CGRP阳性轴突密度显著增加。有趣的是，与表达全长p75NTR的NGF转基因小鼠相比，NGF/p75（-/-）小鼠显示出更多的新轴突生长。免疫组织化学和超微结构分析显示，这种轴突生长不是再生的结果，而是损伤诱导的完整DRG中央突向病变部位发芽。这种侧枝生长仅限于背角的去分化区域，因此我们认为这是脊髓中NGF敏感轴突代偿发芽的一个例子，在缺乏NGF与p75NTR结合的情况下，这种反应得到增强。(c) 2005 Wiley-Liss, Inc。
This study examined the growth capacity of nerve growth factor (NGF)-responsive dorsal root ganglion (DRG) central processes using mice of the following genotypes: wildtype, p75 neurotrophin receptor (p75NTR) exon III null mutant, NGF transgenic, and NGF transgenic with p75NTR exon III null mutation (NGF/p75(-/-)). In wildtype and p75NTR exon III null mutant mice calcitonin gene-related peptide (CGRP) immunoreactivity in the dorsal horn is dramatically reduced at both 3 and 28 days after rhizotomy. NGF transgenic and NGF/p75(-/-) mice also display reduced CGRP immunoreactivity 3 days after rhizotomy, but by postsurgical day 28 significant increases in the density of CGRP-positive axons are observed in the injured dorsal horns of these mice. Interestingly, NGF/p75(-/-) mice displayed significantly more new axonal growth when compared to NGF transgenic mice expressing full-length p75NTR. Immunohistochemical and ultrastructural analyses revealed that this axonal growth is not the result of regeneration but rather injury-induced sprouting by intact DRG central processes into the lesion site. This collateral growth is restricted to deafferentated areas of the dorsal horn, and we therefore propose that this is an example of compensatory sprouting by NGF-sensitive axons in the spinal cord, a response that is enhanced in the absence of NGF binding to p75NTR. (c) 2005 Wiley-Liss, Inc.