Gap junctions (GJs) provide channels for direct cell-to-cell connectivity serving the homeostasis in several organs of vertebrates including the central (CNS) and peripheral (PNS) nervous systems. GJs are composed of connexins (Cx), which show a highly distinct cellular and subcellular expression pattern. Oligodendrocytes, the myelinating cells of the CNS, are characterized by extensive GJ connectivity with each other as well as with astrocytes. The main oligodendrocyte connexins forming these GJ channels are Cx47 and Cx32. The importance of these channels has been highlighted by the discovery of human diseases caused by mutations in oligodendrocyte connexins, manifesting with leukodystrophy or transient encephalopathy. Experimental models have provided further evidence that oligodendrocyte GJs are essential for CNS myelination and homeostasis, while a strong inflammatory component has been recognized in the absence of oligodendrocyte connexins. Further studies revealed that connexins are also disrupted in multiple sclerosis (MS) brain, and in experimental models of induced inflammatory demyelination. Moreover, induced demyelination was more severe and associated with higher degree of CNS inflammation in models with oligodendrocyte GJ deficiency, suggesting that disrupted connexin expression in oligodendrocytes is not only a consequence but can also drive a pro-inflammatory environment in acquired demyelinating disorders such as MS. In this review, we summarize the current insights from human disorders as well as from genetic and acquired models of demyelination related to oligodendrocyte connexins, with the remaining challenges and perspectives.

间隙连接（GJs）提供了直接的细胞间连接通道，从而为脊椎动物的多个器官（包括中枢神经系统（CNS）和周围神经系统（PNS））的体内平衡提供了动力。GJ由连接蛋白（Cx）组成，它们显示出高度不同的细胞和亚细胞表达模式。少突胶质细胞是CNS的髓鞘细胞，其特征是彼此之间以及与星形胶质细胞之间具有广泛的GJ连接性。形成这些GJ通道的主要少突胶质细胞连接蛋白是Cx47和Cx32。通过发现少突胶质细胞连接蛋白突变引起的人类疾病，突显了这些通道的重要性，表现为白细胞营养不良或短暂性脑病。实验模型提供了进一步的证据，表明少突胶质细胞GJ对于中枢神经系统的髓鞘形成和动态平衡至关重要，在缺乏少突胶质细胞连接蛋白的情况下，人们已经认识到强烈的炎症成分。进一步的研究表明，连接蛋白在多发性硬化症（MS）大脑以及诱导性脱髓鞘的实验模型中也被破坏。此外，在少突胶质细胞GJ缺乏的模型中，诱导的脱髓鞘作用更严重，并且与中枢神经系统炎症的程度更高相关，这表明，少突胶质细胞中连接蛋白表达的破坏不仅是后果，而且还可以驱动获得性脱髓鞘疾病（例如MS）的促炎环境。在这篇综述中，我们总结了来自人类疾病以及与少突胶质细胞连接蛋白有关的脱髓鞘的遗传和获得性模型的最新见解，还有其他挑战和观点。