Expression changes of the neuregulin 1 isoforms in neuropathic pain model rats
Expression changes of the neuregulin 1 isoforms in neuropathic pain model rats
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DOI：
10.1016/j.neulet.2011.12.023
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发表时间：
2012-02-06
影响因子：
2.5
通讯作者：
Morita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kanzaki, Hirotaka;Mizobuchi, Satoshi;Morita, Kiyoshi
在背根神经节（DRG）中表达的神经调节蛋白1（Nrg 1）基因含有EGF样结构域，已知其是ErbB 3和ErbB 4的直接配体。Nrg 1基因的多个剪接变体根据结构特征大致分为3组（I型、II型和III型），并且它们的功能在各种组织中不同。Nrg 1基因已成为轴突-许旺细胞相互作用的关键介质，并作为许旺细胞发育的调节因子。Nrg 1基因被认为是神经元发育的一个有前途的生长因子。然而，Nrg 1在疼痛中的功能尚未阐明。因此，我们使用L5脊神经结扎（SNL）模型大鼠和完全弗氏佐剂（CFA）模型大鼠，检查了双侧L4/L5 DRG中每种类型的Nrg 1转录本的表达谱。行为测试显示在L5 SNL模型和CFA模型中均存在典型的机械性痛觉过敏。在L5 SNL模型中，Nrg 1 I型和II型在L5 DRG中的表达显著增加。另一方面，Nrg 1 III型在L5 DRG中的表达减少。我们证明，在同侧背根神经节的Nrg 1亚型的表达变化优先与神经损伤的反应。我们的研究结果表明，异常表达可能在L5 SNL神经损伤，再生和随后的神经病理性疼痛中发挥重要作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The neuregulin1 (Nrg1) gene that is expressed in the dorsal root ganglion (DRG) contains an EGF-like domain, which is known to be a direct ligand for ErbB3 and ErbB4. Multiple splice variants of the Nrg1 gene are broadly classified into 3 groups by structural features (type I, type 11 and type III) and their functions differ in various tissues. The Nrg1 gene has emerged as a key mediator of axon-Schwann cell interactions and as a regulator of Schwann cell development. The Nrg1 gene is indicated as a promising growth factor for neuronal development. However, the function of the Nrg1 in pain has not been clarified. We therefore, examined the expression profiles of each type of the Nrg1 transcript in the bilateral L4/L5 DRGs using L5 spinal nerve ligation (SNL) model rats and complete Freund's adjuvant (CFA) model rats. Behavior tests have shown typical mechanical hyperalgesia in both the L5SNL model and the CFA model. In the L5SNL model, expression of the Nrg1 type I and type II were significantly increased in the L5 DRG. On the other hand, the expression of the Nrg1 type III was decreased in the L5 DRG. We demonstrated that the expression changes of the Nrg1 isoforms in the ipsilateral DRGs were preferentially related to the response to nerve injury. Our findings suggest that the aberrant expression may play an important role in nerve injury, regeneration and subsequent neuropathic pain on the L5SNL. (C) 2011 Elsevier Ireland Ltd. All rights reserved.