Department of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Glia. 2011 Dec;59(12):1841-9. doi: 10.1002/glia.21228. Epub 2011 Sep 1.
The overall morphology and with it associated the formation of myelin is generally thought to be resolved. Based on electron microscopic findings more than half a century ago, the current model of myelination describes all myelin membranes to run in parallel with the longitudinal axis of the axon and to form a smooth surface, reminiscent of a rolled up carpet. However, different studies in the past demonstrated a distinct myelin morphology with an uneven myelin surface contour that challenges the established concept. Even though the current model of myelination has since been recognized as insufficient, CNS myelin formation has not yet been investigated in real-time with the requisite technique and resolution. We therefore traced myelin growth in murine organotypic cerebellar slice cultures using high-resolution confocal live imaging, light and electron microscopy and assessed myelin morphology in young and adult mice by confocal microscopy. Our data verify that the myelin surface is indeed not smooth but runs in a bidirectional, regularly spaced coil along the axon in both young and adult mice. Time-lapse imaging revealed that the growth of coiled myelin turns emerges during myelin formation. We therefore propose the "liquid croissant" model as a new concept of myelination that overcomes not only some of the incongruences of previous myelination theories, but potentially also explains the development of certain myelin pathologies observed in remyelination and axonopathies.
人们普遍认为，整体形态及其相关的髓鞘形成已经得到解决。基于半个多世纪以前的电子显微镜发现，目前的髓鞘形成模型描述了所有的髓鞘膜都与轴突的纵轴平行，并形成一个光滑的表面，让人联想到卷起的地毯。然而，过去的不同研究表明，髓鞘表面轮廓不均匀，具有明显的髓鞘形态，这对既定的概念提出了挑战。尽管髓鞘形成的现行模型已被认为不充分，但中枢神经系统的髓鞘形成尚未采用必要的技术和分辨率进行实时研究。因此，我们使用高分辨率共聚焦活细胞成像、光镜和电镜追踪了鼠器官型小脑切片培养物中的髓鞘生长，并通过共聚焦显微镜评估了幼鼠和成年鼠的髓鞘形态。我们的数据证实，髓鞘表面实际上并不光滑，而是在幼鼠和成年鼠的轴突上呈双向、规则间隔的螺旋状排列。延时成像显示，螺旋形髓鞘的生长是在髓鞘形成过程中出现的。因此，我们提出了“液态羊角面包”模型作为一个新的髓鞘形成概念，不仅克服了以前髓鞘形成理论的一些不一致之处，而且可能还解释了在髓鞘再生和轴突病变中观察到的某些髓鞘病理学的发展。
