Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation
Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation
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DOI：
10.1016/j.expneurol.2005.04.007
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
English, AW
中科院分区：
文献类型：
--
作者：
Groves, ML;McKeon, R;English, AW
去除硫酸软骨素蛋白聚糖的糖胺聚糖侧链 (GAG) 可以增强周围神经系统中轴突的再生。然而，尽管进行了这种治疗，一些轴突再生仍很差，这表明存在额外的抑制剂。我们比较了硫酸软骨素蛋白聚糖与其他两种蛋白聚糖（硫酸乙酰肝素和硫酸角质素蛋白聚糖）中酶促去除 GAG 对外周轴突再生的影响。使用从野生型同窝小鼠中收获的 CF 神经短段切割并修复 thy-1-YFP-H 小鼠的腓总 (CF) 神经，并在神经修复前用 GAG 降解酶预处理 1 小时。 1周后，通过测量移植神经光学切片中YFP+轴突轮廓的长度来测定轴突再生。除了用角化酶处理的移植物外，酶处理的移植物中比对照移植物遇到更多和更长的轴突轮廓。肝素酶 III 处理诱导最大数量的轴突进入移植物。在用软骨素酶ABC或肝素酶1处理的移植物中，长度超过1000μm的轴突轮廓的比例更大，但在用角质酶或肝素酶III处理的移植物中则没有。用肝素酶 I 处理后观察到的再生芽比任何其他酶都多。用所有四种酶的混合物处理导致轴突再生的增强，其大于单独用任何酶处理后观察到的效果。软骨素酶 ABC 和肝素酶 III 的作用与特定的 GAG 降解相关。我们相信，酶促去除 GAG 对于促进再生轴突选择其在远端残端（或神经移植物）中的路径的能力特别有效，并且对于软骨素酶 ABC 或肝素酶 I，它还可能促进该路径内的生长。 (c) 2005 Elsevier Inc. 保留所有权利。
Regeneration of axons in the peripheral nervous system is enhanced by the removal of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans. However, some axons regenerate poorly despite such treatment, suggesting the existence of additional inhibitors. We compared the effects of enzymatic removal of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan species, heparan sulfate and keratan sulfate protcoglycans, on the regeneration of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and repaired using short segments of CF nerves harvested from wild-type littermates and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal regeneration was assayed by measuring the lengths of profiles of YFP+ axons in optical sections of the grafted nerves 1 week later. Except for grafts treated with keratanase, more and longer axon profiles were encountered in enzyme-treated grafts than in control grafts. Heparinase III treatments induced the greatest number of axons to enter into the graft. The proportions of axon profiles longer than 1000 mu m were greater in grafts treated with chondroitinase ABC or heparinase 1, but not with either keratanase or heparinase III. More regenerative sprouts were observed after treatment with heparinase I than any other enzymes. Treatment with a mixture of all four enzymes resulted in an enhancement of axon regeneration which was greater than that observed after treatment with any of the enzymes individually. The effects of chondroitinase ABC and heparinase III were correlated with specific GAG degradation. We believe that enzymatic removal of GAGs is especially effective in promoting the ability of regenerating axons to select their pathway in the distal stump (or nerve graft) and, in the case of chondroitinase ABC or heparinase I, it may also promote growth within that pathway. (c) 2005 Elsevier Inc. All rights reserved.