The adult oligodendrocyte can participate in remyelination
The adult oligodendrocyte can participate in remyelination
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DOI：
10.1073/pnas.1808064115
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发表时间：
2018-12-11
影响因子：
11.1
通讯作者：
Wierenga, Lauren A.
中科院分区：
文献类型：
--
作者：
Duncan, Ian D.;Radcliff, Abigail B.;Wierenga, Lauren A.
中枢神经系统的内源性髓鞘再生可以是强大的，并恢复功能，但在多发性硬化症中，随着时间的推移，它变得不那么完整。促进髓鞘再生是一个主要的治疗目标，既可以恢复功能，又可以保护轴突免于退化。再髓鞘形成被认为依赖于少突胶质细胞祖细胞，产生新生的髓鞘再生少突胶质细胞。存活的成熟少突胶质细胞在很大程度上被认为是不参与的。我们已经用两个大型动物模型研究了这个问题。在第一个模型中，有广泛的脱髓鞘和髓鞘再生的中枢神经系统，但少突胶质细胞存活，并在恢复的动物有一个混合的髓鞘再生轴突之间散布成熟，厚的髓鞘。使用2D和3D光学和电子显微镜，我们发现，许多少突胶质细胞连接到成熟和髓鞘再生的髓鞘，我们的结论是细胞有重新延长的过程接触脱髓鞘轴突，同时保持成熟的髓鞘节间。在维生素B-12缺乏的非人灵长类动物的第二个模型中，我们证明了存活的成熟少突胶质细胞延长了突起并包裹脱髓鞘轴突。这些数据表明，成熟的少突胶质细胞可以参与髓鞘再生。
Endogenous remyelination of the CNS can be robust and restore function, yet in multiple sclerosis it becomes less complete with time. Promoting remyelination is a major therapeutic goal, both to restore function and to protect axons from degeneration. Remyelination is thought to depend on oligodendrocyte progenitor cells, giving rise to nascent remyelinating oligodendrocytes. Surviving, mature oligodendrocytes are largely regarded as being uninvolved. We have examined this question using two large animal models. In the first model, there is extensive demyelination and remyelination of the CNS, yet oligodendrocytes survive, and in recovered animals there is a mix of remyelinated axons interspersed between mature, thick myelin sheaths. Using 2D and 3D light and electron microscopy, we show that many oligodendrocytes are connected to mature and remyelinated myelin sheaths, which we conclude are cells that have reextended processes to contact demyelinated axons while maintaining mature myelin internodes. In the second model in vitamin B-12-deficient nonhuman primates, we demonstrate that surviving mature oligodendrocytes extend processes and ensheath demyelinated axons. These data indicate that mature oligodendrocytes can participate in remyelination.