Myelin-associated glycoprotein reduces axonal branching and enhances functional recovery after sciatic nerve transection in rats
Myelin-associated glycoprotein reduces axonal branching and enhances functional recovery after sciatic nerve transection in rats
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DOI：
10.1002/glia.20566
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发表时间：
2007-11-01
期刊：
影响因子：
6.2
通讯作者：
Hosokawa, Ko
中科院分区：
文献类型：
--
作者：
Tomita, Koichi;Kubo, Tateki;Hosokawa, Ko
与中枢神经系统（CNS）相比，成熟的外周神经系统（PNS）通常显示出更好的受损轴突再生。然而，即使在PNS中也很少实现完全的功能恢复，尽管经常发生形态学良好的轴突再生。这主要是由于切断轴突的广泛分支导致肌肉同步运动失败而导致的异常神经再支配。髓鞘相关糖蛋白（MAG）是一种广泛存在于中枢神经系统和PNS髓鞘中的分子，被认为是中枢神经系统轴突再生的有效抑制剂。在本研究中，我们调查是否MAG有任何影响，不仅对轴突伸长，但也对轴突分支。我们在此表明，MAG最小化的外周轴突的分支在体外和体内通过激活RhoA。此外，大鼠坐骨神经切断后，局部和暂时应用MAG的病变显着提高了功能恢复。使用双逆行标记和术前/术后标记脊髓神经元，减少过度神经支配和提高目标神经再支配的准确性分别得到证实。总之，由于MAG显著提高了轴突再生的质量，因此它可以作为一种新的治疗方法用于周围神经修复，具有可能的局部和暂时应用。(C)2007 Wiley-Liss，Inc.
The mature peripheral nervous system (PNS) generally shows better regeneration of injured axons as opposed to the central nervous system (CNS). However, complete functional recovery is rarely achieved even in the PNS although morphologically good axonal regeneration often occurs. This mainly results from aberrant reinnervation due to extensive branching of cut axons with consequent failure of synchronized movements of the muscles. Myelin-associated glycoprotein (MAG), a well-characterized molecule existing both in the CNS and PNS myelin, is considered to be a potent inhibitor of axonal regeneration especially in the CNS. In the present study, we investigated whether MAG has any effects not only on axonal elongation, but also on axonal branching. We show herein that MAG minimized branching of the peripheral axons both in vitro and in vivo via activation of RhoA. Furthermore, after sciatic nerve transection in rats, focal and temporary application of MAG to the lesion dramatically enhanced the functional recovery. Using double retrograde labeling and preoperative/postoperative labeling of spinal neurons, reduced hyperinnervation and improved accuracy of target reinnervation was confirmed, respectively. In conclusion, as MAG significantly improves the quality of axonal regeneration, it can be used as a new therapeutic approach for peripheral nerve repair with possible focal and temporary application. (C) 2007 Wiley-Liss, Inc.