In the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated in the stability of axo-oligodendroglial paranodal junctions. Here we report that the netrin receptor UNC5B is highly expressed by mature oligodendrocytes and enriched at paranodes. We demonstrate that paranodes become disorganized following conditional deletion of UNC5B in oligodendrocytes, with disruption of the interface between glial loops and detachment of loops from the axon. As a result, Caspr1 and Kv1.1 disperse along the axon, internodes fail to lengthen and compact myelin periodicity is reduced. Paranodal and axoglial domain disorganization progressively worsens and a delay in motor learning develops in aged mice lacking oligodendroglial UNC5B. Altered glial loop ultrastructure and reduced levels of claudin-11 and JAM-C tight junction proteins support the conclusion that disruption of autotypic junctions between paranodal loops underlies paranode disorganization. Our findings reveal an essential contribution of oligodendroglial UNC5B at paranodes that is required for the stability of mature myelin.

中文翻译：

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旁节稳定性需要少突胶质细胞表达UNC5B

在成熟的中枢神经系统中，netrin-1由神经元和少突胶质细胞表达，并涉及轴突-少突胶质神经节旁结的稳定性。在这里我们报告说，netrin受体UNC5B由成熟的少突胶质细胞高度表达并富集在节旁。我们证明，节旁神经元在少突胶质细胞中有条件的UNC5B缺失后变得杂乱无章，与神经胶质环和从轴突环分离之间的接口的破坏。结果，Caspr1和Kv1.1沿着轴突分散，节间无法延长，紧凑的髓磷脂周期性降低。在缺乏少突神经胶质UNC5B的老年小鼠中，旁侧和轴突区域的组织紊乱逐渐恶化，并且运动学习延迟出现。改变的神经胶质环超微结构和降低的claudin-11和JAM-C紧密连接蛋白水平支持以下结论，即结旁环之间的自发性连接破坏是结节杂乱的基础。我们的发现揭示了少突神经胶质UNC5B在节旁的重要贡献，这是成熟髓磷脂的稳定性所必需的。