Colello R J, Pott U, Schwab M E
Brain Research Institute, University of Zürich, Switzerland.
J Neurosci. 1994 May;14(5 Pt 1):2594-605. doi: 10.1523/JNEUROSCI.14-05-02594.1994.
In neonatal mammals, newly grown optic axons are uniformly small in diameter. In the adult, in contrast, axons within the optic nerve can be classified into distinct groups according to their diameter. Because axon diameters are also related to the thickness of the myelin sheath, which in turn determines the velocity of action potential propagation, the question of what determines the axon diameter is of critical importance. In a project aimed at determining the influence of the ensheathing cell on axon maturation, oligodendrocyte development was prevented by eliminating their precursors by unilateral x-irradiation at birth. Axon diameters in both the normal and the myelin-free optic nerves were then measured at varying stages of development. The results demonstrate that axon diameter growth remained substantially reduced in the absence of oligodendrocytes. Interestingly, by x-irradiating the optic nerve and tract on one side of the brain, fibers crossing the chiasm became larger as they went from an unmyelinated nerve to a myelinated tract; fibers on the nonirradiated side became smaller as they went from a myelinated nerve and crossed into the nonmyelinated tract. These results clearly point to a local regulation of axon diameter by oligodendrocytes. Moreover, ganglion cells measured 9 d after the initiation of myelination (postnatal day 6, P6) were of similar size within normal retinas and retinas whose axons were x-irradiated, suggesting that ganglion cell growth occurs in spite of the lack of myelin and axon diameter maturation. Finally, we showed, through both section staining with antibodies to myelin basic protein (MBP) and Northern blot analysis using a probe to MBP, that the x-irradiated nerve began a delayed myelination period (in a gradient from chiasm to eye) at P15 and reached an almost normal myelin pattern at P28. Axons from these nerves grew to seemingly normal diameter concomitant with this delayed myelination.
在新生哺乳动物中，新生长的视神经轴突直径一致较小。相比之下，在成年动物中，视神经内的轴突可根据其直径分为不同的组。由于轴突直径也与髓鞘厚度相关，而髓鞘厚度又决定了动作电位的传播速度，因此确定轴突直径的决定因素这一问题至关重要。在一个旨在确定包绕细胞对轴突成熟影响的项目中，通过在出生时单侧X射线照射消除少突胶质细胞前体，从而阻止少突胶质细胞的发育。然后在不同发育阶段测量正常和无髓鞘视神经中的轴突直径。结果表明，在少突胶质细胞缺失的情况下，轴突直径的生长仍大幅减少。有趣的是，通过对大脑一侧的视神经和视束进行X射线照射，穿过视交叉的纤维从无髓鞘神经进入有髓鞘束时会变得更大；未照射侧的纤维从有髓鞘神经进入无髓鞘束时会变得更小。这些结果清楚地表明少突胶质细胞对轴突直径有局部调节作用。此外，在髓鞘形成开始后9天（出生后第6天，P6）测量的神经节细胞，在正常视网膜和轴突接受X射线照射的视网膜中大小相似，这表明尽管缺乏髓鞘和轴突直径成熟，神经节细胞仍能生长。最后，我们通过用髓鞘碱性蛋白（MBP）抗体进行切片染色以及使用MBP探针进行Northern印迹分析均表明，接受X射线照射的神经在P15开始延迟髓鞘形成期（从视交叉到眼睛呈梯度变化），并在P28达到几乎正常的髓鞘模式。来自这些神经的轴突随着这种延迟的髓鞘形成而生长到看似正常的直径。
