Department of Physiology, Third Military Medical University, Chongqing 400038, China.
Mol Neurobiol. 2013 Apr;47(2):845-56. doi: 10.1007/s12035-013-8408-8. Epub 2013 Jan 24.
Myelination by oligodendrocytes facilitates rapid nerve conduction. Loss of oligodendrocytes and failure of myelination lead to nerve degeneration and numerous demyelinating white matter diseases. N-methyl-D-aspartate (NMDA) receptors, which are key regulators on neuron survival and functions, have been recently identified to express in oligodendrocytes, especially in the myelin sheath. NMDA receptor signaling in oligodendrocytes plays crucial roles in energy metabolism and myelination. In the present review, we highlight the subcellular location-specific impairment of excessive NMDA receptor signaling on oligodendrocyte energy metabolism in soma and myelin, and the mechanisms including Ca(2+) overload, acidotoxicity, mitochondria dysfunction, and impairment of respiratory chains. Conversely, physiological NMDA receptor signaling regulates differentiation and migration of oligodendrocytes. How can we use above knowledge to treat excitotoxic oligodendrocyte loss, congenital myelination deficiency, or postnatal demyelination? A thorough understanding of NMDA receptor signaling-mediated cellular events in oligodendrocytes at the pathophysiological level will no doubt aid in exploring effective therapeutic strategies for demyelinating white matter diseases.
少突胶质细胞的髓鞘形成有助于神经快速传导。少突胶质细胞的丧失和髓鞘形成失败会导致神经变性和许多脱髓鞘的白质疾病。最近发现 N-甲基-D-天冬氨酸（NMDA）受体在少突胶质细胞中表达，特别是在髓鞘中。NMDA 受体信号在少突胶质细胞的能量代谢和髓鞘形成中起着关键作用。在本综述中，我们强调了 NMDA 受体信号在胞体和髓鞘中过度表达对少突胶质细胞能量代谢的亚细胞定位特异性损伤，以及包括钙超载、酸中毒、线粒体功能障碍和呼吸链损伤在内的机制。相反，生理 NMDA 受体信号调节少突胶质细胞的分化和迁移。我们如何利用上述知识来治疗兴奋性少突胶质细胞丧失、先天性髓鞘形成缺陷或后天性脱髓鞘？深入了解 NMDA 受体信号在病理生理水平上介导的少突胶质细胞中的细胞事件，无疑将有助于探索脱髓鞘白质疾病的有效治疗策略。
