Savio T, Schwab M E
Brain Research Institute, University of Zurich, Switzerland.
J Neurosci. 1989 Apr;9(4):1126-33. doi: 10.1523/JNEUROSCI.09-04-01126.1989.
In adult mammalian CNS, axons mostly fail to regenerate after injury, while in the PNS they often succeed in reaching their previous targets. Crucial differences are present in the local tissue microenvironment of CNS and PNS. To investigate the substrate properties of nervous tissue for neuronal adhesion and fiber growth, we used frozen sections of rat CNS and PNS as culture substrates for neuroblastoma cells and for sympathetic and dorsal root ganglia. The results showed that CNS white matter from adult rat spinal cord, cerebellum, forebrain, or optic nerve did not allow cell adhesion and axonal elongation. In contrast, gray matter areas, sciatic nerve, and also trout CNS white and gray matter were permissive substrates. To delineate the tissue components of white matter involved in this nonpermissive substrate effect, newborn rats were injected for 13 d with the antimitotic agent 5-azacytidine. This treatment strongly reduced the oligodendrocyte population and the myelin content of the spinal cord. The immunoreactivity for specific oligodendrocyte and astrocyte markers confirmed the selective suppression of oligodendroglia in these rats. Neuroblastoma cells plated on spinal cord sections taken from these animals were no longer exclusively localized on the gray matter but were also found on regions normally rich in myelin. A significant reduction of the white matter nonpermissive substrate effect was also obtained by the monoclonal antibody IN-1 directed against 2 defined myelin proteins with inhibitory substrate properties (Caroni and Schwab, 1988b). Our results, therefore, show that, in the adult mammalian CNS, cell adhesion and axonal elongation are prevented by white matter components, which are, at least in part, associated with oligodendrocytes and myelin.
在成年哺乳动物的中枢神经系统(CNS)中,轴突在损伤后大多无法再生,而在周围神经系统(PNS)中它们常常能够成功抵达先前的靶点。CNS和PNS的局部组织微环境存在关键差异。为了研究神经组织对神经元黏附和纤维生长的底物特性,我们使用大鼠CNS和PNS的冰冻切片作为神经母细胞瘤细胞以及交感神经节和背根神经节的培养底物。结果显示,成年大鼠脊髓、小脑、前脑或视神经的CNS白质不允许细胞黏附和轴突伸长。相比之下,灰质区域、坐骨神经以及鳟鱼的CNS白质和灰质都是允许性底物。为了确定参与这种非允许性底物效应的白质组织成分,给新生大鼠注射抗有丝分裂剂5-氮杂胞苷,持续13天。这种处理显著减少了脊髓中少突胶质细胞的数量和髓磷脂含量。针对特定少突胶质细胞和星形胶质细胞标志物的免疫反应性证实了这些大鼠中少突胶质细胞的选择性抑制。接种在取自这些动物的脊髓切片上的神经母细胞瘤细胞不再仅局限于灰质,在通常富含髓磷脂的区域也能发现。针对具有抑制性底物特性的2种特定髓磷脂蛋白的单克隆抗体IN-1也显著降低了白质的非允许性底物效应(卡罗尼和施瓦布,1988b)。因此,我们的结果表明,在成年哺乳动物CNS中,白质成分阻止了细胞黏附和轴突伸长,这些白质成分至少部分与少突胶质细胞和髓磷脂有关。