Regeneration of nigrostriatal dopaminergic axons by degradation of chondroitin sulfate is accompanied by elimination of the fibrotic scar and glia limitans in the lesion site
Regeneration of nigrostriatal dopaminergic axons by degradation of chondroitin sulfate is accompanied by elimination of the fibrotic scar and glia limitans in the lesion site
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通过硫酸软骨素的降解实现黑质纹状体多巴胺能轴突的再生，同时消除病变部位的纤维化疤痕和神经胶质细胞界限
DOI：
10.1002/jnr.21141
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发表时间：
2007-02-15
影响因子：
4.2
通讯作者：
Kawano, Hitoshi
中科院分区：
文献类型：
--
作者：
Li, Hong-Peng;Homma, Akiko;Kawano, Hitoshi
中枢神经系统损伤后，病变部位周围的硫酸软骨素增加，并且被认为是轴突再生的障碍，因为施用硫酸软骨素降解酶 ABC 可以促进中枢神经元的轴突再生。为了检查损伤后硫酸软骨素上调的生理作用，单侧横断小鼠黑质纹状体多巴胺能轴突，然后将软骨素酶ABC注射到病变部位。仅在横切小鼠中，横切后 1 或 2 周时，酪氨酸羟化酶免疫反应性轴突并未延伸穿过病变部位。病灶部位及其周围的硫酸软骨素侧链和NG2蛋白聚糖核心蛋白的免疫反应性增加，病灶中心出现含有IV型胶原沉积物的纤维化疤痕。相比之下，在横切并用软骨素酶 ABC 处理的小鼠中，横切后 1 周和 2 周，大量酪氨酸羟化酶免疫反应性轴突在病变处再生。在这些动物中，硫酸软骨素的免疫反应性显着降低，而识别降解的硫酸软骨素侧链残端的2136抗体的免疫反应性则增强。此外，纤维化疤痕和围绕前者的神经胶质细胞的形成被完全阻止，尽管IV型胶原免疫反应性仍然存在于病变部位周围新形成的毛细血管中。我们讨论硫酸软骨素是否作为轴突再生的直接抑制剂，或者观察到的变化是否是由于防止纤维化疤痕形成和星形胶质细胞膜重新排列所致。 (c) 2006 Wiley-Liss, Inc.
Chondroitin sulfate increases around a lesion site after central nervous system injury and is believed to be an impediment to axonal regeneration, because administration of chondroitinase ABC, a chondroitin sulfate-degrading enzyme, promotes axonal regeneration of central neurons. To examine the physiological role of chondroitin sulfate up-regulation after injury, the nigrostriatal doparninergic axons were unilaterally transected in mice, and chondroitinase ABC was then injected into the lesion site. In mice transected only, tyrosine hydroxylase-immunoreactive axons did not extend across the lesion at 1 or 2 weeks after the transection. Immunoreactivities of chondroitin sulfate side chains and core protein of NG2 proteoglycan increased in and around the lesion site, and a fibrotic scar containing type IV collagen deposits developed in the lesion center. In contrast, in mice transected and treated with chondroitinase ABC, numerous tyrosine hydroxylase-immunoreactive axons were regenerated across the lesion at 1 and 2 weeks after the transection. In these animals, chondroitin sulfate immunoreactivity remarkably decreased, and immunoreactivity of 2136 antibody, which recognizes the stub of degraded chondroitin sulfate side chains, was enhanced. Furthermore, the formation of a fibrotic scar and a glia limitans that surrounds the former was completely prevented, although type IV collagen immunoreactivity remained in newly formed blood capillaries around the lesion site. We discuss the question of whether the chondroitin sulfate is acting as a direct inhibitor of axonal regeneration or whether the observed changes are due to a prevention of the fibrotic scar formation and a rearrangement of astrocytic membranes. (c) 2006 Wiley-Liss, Inc.