Kidd G J, Heath J W
Neuroscience Group, Faculty of Medicine, University of Newcastle, New South Wales, Australia.
J Neurosci. 1991 Dec;11(12):4003-14. doi: 10.1523/JNEUROSCI.11-12-04003.1991.
Axonal contact plays a critical role in initiating myelin formation by Schwann cells. However, recent studies of "double myelination" have indicated that myelin maintenance continues in Schwann cells completely displaced from physical contact with the axon. This raises the possibility either that diffusible trophic factors are produced by the axon, or that the axon is not required for myelin maintenance by these displaced Schwann cells. To test these hypotheses, the axons involved in double myelination in the mouse superior cervical ganglion (SCG) were transected surgically by a transganglionic lesion. The inferior pole of the SCG was resected to limit axonal regeneration. This method produced a typical Wallerian pattern of degeneration in the superior pole, without compromising the blood supply or introducing nonspecific trauma. EM analysis at 1 and 5 d postoperatively showed that initially the axon degenerated, followed by breakdown of the inner myelin sheath. In those configurations where the outer Schwann cell was only partly displaced from the axon, the outer myelin sheath degenerated simultaneously. However, in completely displaced internodes the outer sheath survived degeneration of the axon and inner sheath. Outer internodes remained intact for at least 5 weeks after transection (the longest time point in this study), at which time they enclosed reorganized processes of the inner Schwann cells, their basal lamina, and numerous collagen fibrils. Axonal regeneration within surviving outer internodes was rare and was characterized by the development of typical Remak ensheathment by the inner Schwann cells. We conclude that in the mouse SCG, myelin maintenance does not depend on the continued presence of the axon. These data suggest further that myelin breakdown in Wallerian degeneration may be initiated by mechanisms other than absence of a viable axon.
轴突接触在启动施万细胞形成髓鞘的过程中起着关键作用。然而，最近关于“双重髓鞘形成”的研究表明，与轴突完全脱离物理接触的施万细胞中髓鞘维持仍在继续。这就提出了两种可能性，要么轴突产生了可扩散的营养因子，要么这些脱离接触的施万细胞维持髓鞘不需要轴突。为了验证这些假设，通过跨神经节损伤手术切断了小鼠颈上神经节（SCG）中参与双重髓鞘形成的轴突。切除SCG的下极以限制轴突再生。该方法在上极产生了典型的华勒氏变性模式，而不影响血液供应或引入非特异性损伤。术后1天和5天的电镜分析表明，最初轴突退化，随后内髓鞘崩解。在那些外施万细胞仅部分与轴突脱离的结构中，外髓鞘同时退化。然而，在完全脱离的节段中，外鞘在轴突和内鞘退化后仍存活。切断后外节段至少5周保持完整（本研究中的最长时间点），此时它们包裹着内施万细胞的重组突起、其基膜和许多胶原纤维。存活的外节段内轴突再生很少见，其特征是内施万细胞形成典型的雷马克氏髓鞘。我们得出结论，在小鼠SCG中，髓鞘维持不依赖于轴突的持续存在。这些数据进一步表明，华勒氏变性中的髓鞘崩解可能由除缺乏有活力的轴突之外的其他机制引发。
