Wallquist Wilhelm, Zelano Johan, Plantman Stefan, Kaufman Stephen J, Cullheim Staffan, Hammarberg Henrik
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Comp Neurol. 2004 Dec 6;480(2):162-9. doi: 10.1002/cne.20345.
The favorable prognosis of regeneration in the peripheral nervous system after axonal lesions is generally regarded as dependent on the Schwann cell basal lamina. Laminins, a heterotrimeric group of basal lamina molecules, have been suggested to be among the factors playing this supportive role. For neurons to utilize laminin as a substrate for growth, an expression of laminin binding receptors, integrins, is necessary. In this study, we have examined the expression of laminin binding integrin subunits in dorsal root ganglion (DRG) neurons after transection to either their peripherally projecting axons, as in the sciatic nerve, followed by regeneration, or the centrally projecting axons in dorsal roots, followed by no or weak regenerative activity. In uninjured DRG, immunohistochemical staining revealed a few neurons expressing integrin subunit alpha6, whereas integrin subunits alpha7 and foremost beta1 were expressed in a majority of neurons. After an injury to the sciatic nerve, mRNAs encoding all three integrins were up-regulated in DRG neurons. By anterograde tracing, immunoreactivity for all studied integrins was also found in association with growing axons after a sciatic nerve crush lesion in vivo. In contrast, mRNA levels remained constant in DRG neurons after a dorsal root injury. Together with previous findings, this suggests that integrin subunits alpha6, alpha7, and beta1 have an important role in the regenerative response following nerve injury and that the lack of regenerative capacity following dorsal root injury could in part be explained by the absence of response in integrin regulation.
轴突损伤后外周神经系统再生的良好预后通常被认为依赖于施万细胞基膜。层粘连蛋白是基膜分子的异源三聚体基团,被认为是发挥这种支持作用的因素之一。为了使神经元将层粘连蛋白用作生长底物,层粘连蛋白结合受体整合素的表达是必要的。在本研究中,我们检测了背根神经节(DRG)神经元在其外周投射轴突(如坐骨神经)横断后再生,或在背根中中枢投射轴突横断后无再生或再生微弱情况下,层粘连蛋白结合整合素亚基的表达。在未受伤的DRG中,免疫组织化学染色显示少数神经元表达整合素亚基α6,而整合素亚基α7以及主要是β1在大多数神经元中表达。坐骨神经损伤后,DRG神经元中编码所有三种整合素的mRNA均上调。通过顺行追踪,在体内坐骨神经挤压损伤后,还发现所有研究的整合素的免疫反应性与生长的轴突相关。相比之下,背根损伤后DRG神经元中的mRNA水平保持不变。与先前的研究结果一起,这表明整合素亚基α6、α7和β1在神经损伤后的再生反应中起重要作用,并且背根损伤后再生能力的缺乏部分可以通过整合素调节无反应来解释。