CGRP peptide and regenerating sensory axons

CGRP peptide and regenerating sensory axons
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DOI:
10.1093/jnen/63.10.1092
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发表时间:
2004-10-01
影响因子:
3.2
通讯作者:
Zochodne, DW
Zochodne, DW
中科院分区:
医学4区
文献类型:
--
作者:
Li, XQ;Verge, VMK;Zochodne, DW

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降钙素基因相关肽是感觉神经元中广泛表达的一种成分,在神经功能和轴突切断后的修复中发挥重要作用。CGRP合成减少,但在切断的轴突终茎中仍有多肽积累。在这项工作中,我们探索了CGRP多肽在再生感觉神经轴突萌芽中的明显选择性和持续表达。在大鼠腓肠神经损伤后14天,再生和分支的感觉神经轴突有强烈和选择性的CGRP表达,与终球无关。然而,亲代L4和L5核膜和腓肠神经近端的轴突并没有表现出如此高的CGRP的存在。取而代之的是,用荧光金或二氨基黄对再生轴突进行反向标记,以减少CGRP的表达。类似地,ATF-3,一个强大的轴突切断神经元的标志物,与α-CGRP mRNA的表达减少有关,而不是与增加相关。然而,出乎意料的是,我们发现了一个扩大的未损伤神经元的次级群体,通常较小,突出到背角,新的和高强度的CGRP表达,但没有ATF-3或示踪剂标记。远端再生的感觉轴突选择性地表达CGRP多肽,而不考虑核周含量的减少,这一现象不能用简单的积累来解释。然而,受损的邻近神经元也可能矛盾地改变CGRP在完整神经元中的表达方式。
CGRP peptide, a widely expressed constituent of sensory neurons, plays important roles in nerve function and repair when axons are severed. CGRP synthesis declines, yet peptide nonetheless accumulates in severed axon endbulbs. In this work we explore an apparent selective and ongoing expression of CGRP peptide in regenerative sensory axon sprouts. Following sural nerve crush in rats out to 14 days, regenerating and branching sensory axons had intense and selective expression of CGRP, not associated with endbulbs. Parent L4 and L5 perikarya and axons in the sural nerve proximal to crush, however, did not exhibit such heightened CGRP presence. Instead, back labeling of regenerating axons with fluorogold or diamidino yellow labeled perikarya with reduced CGRP expression. Similarly, ATF-3, a robust marker of axotomized neurons, was associated with reduced, rather than elevated expression of alphaCGRP mRNA. Unexpectedly, however, we identified an enlarged secondary population of intact uninjured neurons, frequently smaller and projecting to the dorsal horn with new and heightened intense CGRP expression but not ATF-3- or tracer-labeled. Distal regenerating sensory axons selectively express CGRP peptide despite reduced perikaryal content, a phenomenon not explained by simple accumulation. Having an injured neighbor neuron, however, may also paradoxically alter how CGRP is expressed in intact neurons.