在神经损伤和修复过程中,Wallerian溃变为神经再生创造了有利的条件。目前尽管对大鼠坐骨神经损伤后Wallerian溃变过程中远端神经组织的基因表达已有了深入的报道,但相关基因的作用机制尚不明确。

南通大学姚登兵博士所在团队运用基因芯片本课题Affymetrix表达谱芯片服务由上海伯豪生物技术有限公司提供)、生物信息学等技术,全面系统地分析大鼠坐骨神经损伤后Wallerian溃变过程中近远端神经组织的差异基因表达及其参与的信号通路和作用机制的改变。

基因芯片分析结果显示,大鼠坐骨神经损伤后7-14 d在近远端神经组织中有6,000多个差异基因有表达,主要包括神经元分化、神经发育和再生、细胞因子合成、轴突再生等相关基因,主要涉及细胞应激反应、细胞凋亡、炎症反应、免疫反应、信号转导、细胞增殖等个生物学过程。

作者鉴定了其中4个基因-水通道蛋白4、白细胞介素1受体蛋白1、基质金属蛋白酶12和编码许旺细胞的成髓鞘蛋白PRX,结果与上述基因芯片分析结果一致。文章为进一步从分子水平深入研究Wallerian溃变,促进神经修复与再生手段提供了理论基础。相关文章发表于《中国神经再生研究(英文版)》杂志2014年6月第12期。

文章来源:生物帮

原文出处:

Differential gene expression in proximal and distal nerve segments of rats with sciatic nerve injury during Wallerian degeneration

Abstract:

Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves undergoing Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identified, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inflammatory response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were verified for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metalloproteinase-12 and periaxin. Our study identifies differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration.