Fok-Seang J, Smith-Thomas L C, Meiners S, Muir E, Du J S, Housden E, Johnson A R, Faissner A, Geller H M, Keynes R J
Physiological Laboratory, University of Cambridge, UK.
Brain Res. 1995 Aug 21;689(2):207-23. doi: 10.1016/0006-8993(95)00575-b.
The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin and N-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.
成年哺乳动物的中枢神经系统（CNS）缺乏支持轴突再生的能力。越来越多的证据表明，星形胶质细胞作为中枢神经系统中的主要神经胶质细胞群体，可能同时具有促进轴突生长和抑制轴突生长的特性，而后者可能导致中枢神经系统再生能力较差。为了研究允许轴突生长的星形胶质细胞和抑制轴突生长的星形胶质细胞之间的分子差异，我们构建并分析了一组表现出一系列轴突生长促进特性的星形胶质细胞系。在这些星形胶质细胞系的轴突生长促进特性与以下方面之间未发现明显相关性：（i）已知的神经突生长促进分子如层粘连蛋白、纤连蛋白和N-钙黏蛋白的表达；（ii）已知的抑制分子如腱生蛋白和硫酸软骨素蛋白聚糖的表达；（iii）纤溶酶原激活剂和纤溶酶原激活剂抑制剂活性；以及（iv）生长锥塌陷活性。然而，对由星形胶质细胞系形成的聚集体进行的电镜研究表明，与抑制性更强的星形胶质细胞系相关的细胞外基质物质大量存在。当评估星形胶质细胞系沉积的基质的轴突生长促进活性时，发现允许性细胞系的基质是良好的底物，而抑制性星形胶质细胞系的基质则是神经突生长的不良底物。综合我们的研究结果表明，允许性和抑制性星形胶质细胞系之间的功能差异主要存在于细胞外基质中。
