Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Electron Microscopy Core Unit, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Nat Commun. 2022 Mar 4;13(1):1163. doi: 10.1038/s41467-022-28720-y.
Myelin, the electrically insulating sheath on axons, undergoes dynamic changes over time. However, it is composed of proteins with long lifetimes. This raises the question how such a stable structure is renewed. Here, we study the integrity of myelinated tracts after experimentally preventing the formation of new myelin in the CNS of adult mice, using an inducible Mbp null allele. Oligodendrocytes survive recombination, continue to express myelin genes, but they fail to maintain compacted myelin sheaths. Using 3D electron microscopy and mass spectrometry imaging we visualize myelin-like membranes failing to incorporate adaxonally, most prominently at juxta-paranodes. Myelinoid body formation indicates degradation of existing myelin at the abaxonal side and the inner tongue of the sheath. Thinning of compact myelin and shortening of internodes result in the loss of about 50% of myelin and axonal pathology within 20 weeks post recombination. In summary, our data suggest that functional axon-myelin units require the continuous incorporation of new myelin membranes.
髓鞘是轴突的电绝缘鞘，随时间发生动态变化。然而，它是由具有长寿命的蛋白质组成的。这就提出了这样一个稳定的结构如何被更新的问题。在这里，我们研究了在成年小鼠的中枢神经系统中实验性地阻止新髓鞘形成后，使用诱导型 Mbp 缺失等位基因，髓鞘化轨迹的完整性。少突胶质细胞在重组后存活下来，继续表达髓鞘基因，但它们不能维持紧凑的髓鞘鞘。我们使用 3D 电子显微镜和质谱成像技术可视化了未能向轴突侧、最突出的是近旁节段内并入的类髓鞘膜。髓鞘样小体的形成表明，在轴突侧和鞘的内舌部存在现有髓鞘的降解。致密髓鞘变薄和节段缩短导致重组后 20 周内约 50%的髓鞘和轴突病变丢失。总之，我们的数据表明，功能轴突-髓鞘单位需要不断地掺入新的髓鞘膜。
