Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans
Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans
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DOI：
10.1523/jneurosci.19-20-08979.1999
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发表时间：
1999-10-15
影响因子：
5.3
通讯作者：
Bandtlow, CE
中科院分区：
文献类型：
--
作者：
Niederöst, BP;Zimmermann, DR;Bandtlow, CE
损伤的哺乳动物CNS中纤维再生的缺乏受到几种不同因素和机制的影响。除了损伤部位周围形成的胶质瘢痕组织的非有益性质之外，CNS髓鞘中存在的并由少突胶质细胞表达的单个分子，如NI-35/NI-250、bNI-220和髓鞘相关糖蛋白（MAG），已被分离并显示出抑制轴突生长。在这里，我们报告了一个额外的神经突生长抑制活性纯化的牛脊髓髓磷脂是不相关的bNI-220或MAG。这种活动可以归因于存在两个硫酸软骨素蛋白聚糖（CSPGs），短蛋白聚糖和脑特异性多功能蛋白聚糖V2剪接变体。在体外的新生小脑颗粒细胞和背根神经节神经元的神经突起生长强烈抑制这种髓鞘馏分丰富的CSPGs。免疫组化染色显示，短蛋白聚糖和多功能蛋白聚糖V2是目前的表面分化少突胶质细胞。我们提供的证据表明，治疗少突胶质细胞的蛋白聚糖合成抑制剂β-木糖苷可以强烈影响少突胶质细胞的生长许可。β-木糖苷消除了短蛋白聚糖和多功能蛋白聚糖V2的细胞表面呈递，并逆转了与少突胶质细胞相遇时的生长锥塌陷，如延时视频显微镜所示。相反，生长锥能够沿着甚至进入少突胶质细胞的突起生长。我们的研究结果强烈表明，短蛋白聚糖和多能蛋白聚糖V2是中枢神经系统髓鞘的额外成分，有助于其非允许性基质特性轴突生长。这些CSPGs在少突胶质细胞上的表达可能表明它们参与了成年CNS结构可塑性和再生的限制。
The absence of fiber regrowth in the injured mammalian CNS is influenced by several different factors and mechanisms. Besides the nonconducive properties of the glial scar tissue that forms around the lesion site, individual molecules present in CNS myelin and expressed by oligodendrocytes, such as NI-35/NI-250, bNI-220, and myelin-associated glycoprotein (MAG), have been isolated and shown to inhibit axonal growth. Here, we report an additional neurite growth-inhibitory activity purified from bovine spinal cord myelin that is not related to bNI-220 or MAG. This activity can be ascribed to the presence of two chondroitin sulfate proteoglycans (CSPGs), brevican and the brain-specific versican V2 splice variant. Neurite outgrowth of neonatal cerebellar granule cells and of dorsal root ganglion neurons in vitro was strongly inhibited by this myelin fraction enriched in CSPGs. Immunohistochemical staining revealed that brevican and versican V2 are present on the surfaces of differentiated oligodendrocytes. We provide evidence that treatment of oligodendrocytes with the proteoglycan synthesis inhibitors beta-xylosides can strongly influence the growth permissiveness of oligodendrocytes. beta-Xylosides abolished cell surface presentation of brevican and versican V2 and reversed growth cone collapse in encounters with oligodendrocytes as demonstrated by time-lapse video microscopy. Instead, growth cones were able to grow along or even into the processes of oligodendrocytes. Our results strongly suggest that brevican and versican V2 are additional components of CNS myelin that contribute to its nonpermissive substrate properties for axonal growth. Expression of these CSPGs on oligodendrocytes may indicate that they participate in the restriction of structural plasticity and regeneration in the adult CNS.