Age-specific localization of NMDA receptors on oligodendrocytes dictates axon function recovery after ischemia.
Age-specific localization of NMDA receptors on oligodendrocytes dictates axon function recovery after ischemia.
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DOI：
10.1016/j.neuropharm.2015.09.015
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发表时间：
2016-11
影响因子：
4.7
通讯作者：
Baltan S
中科院分区：
文献类型：
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作者：
Baltan S
少突胶质细胞和轴突是缺血性白色物质损伤的主要靶点，并且由此导致的轴突功能丧失是中风存活患者的临床残疾的基础。缺血性损伤的细胞机制随着年龄的变化而变化，这与白色物质中年龄介导的结构变化一致。较短的损伤时间会导致轴突功能的快速和强烈丧失以及广泛的少突胶质细胞死亡。虽然NMDA受体的阻断不能使轴突功能受益，但缺血期间细胞外Ca 2+的去除显著促进年轻白色物质中轴突功能的恢复。然而，这些相同的方法阻碍轴突功能恢复，并且不能保护老化白色物质中的少突胶质细胞。NMDA受体的专性GluN 1亚基表现出年龄特异性表达模式，在年轻成人白色物质中，它主要位于少突胶质细胞体上，而在老化的白色物质中，它也在髓鞘突起上观察到。这种年龄依赖性的重新定位和再分配模式模仿GluN 1的表达过程中观察到的发展，但在相反的顺序。在发育过程中，GluN 1免疫反应从出生后第4-11天（P4-11）的星形胶质细胞运输到P12-18的髓鞘突起和P19-21的少突胶质细胞胞体。虽然未成熟的轴突对缺血更具抵抗力，但在P4-11和P12-18缺血期间阻断NMDA受体会阻碍轴突功能恢复，而不能使P19-21的轴突受益。因此，年龄特异性表达模式的NMDA受体定位似乎调节可塑性的少突胶质细胞和髓鞘缺血作为一个功能的年龄在白色的问题。
Oligodendrocytes and axons are the main targets of an ischemic white matter injury and the resultant loss of axon function underlies the clinical disability in patients who survive a stroke. The cellular mechanisms of ischemic injury change as a function of age in concordance with age-mediated structural changes in white matter. Shorter periods of injury cause rapid and robust loss of axon function together with widespread oligodendrocyte death. While blockade of NMDA receptors fails to benefit axon function, removal of extracellular Ca2+ during ischemia remarkably promotes axon function recovery in young white matter. However, these same approaches hinder axon function recovery and fail to protect oligodendrocytes in aging white matter. The obligatory GluN1 subunit of the NMDA receptor exhibits an age-specific expression pattern such that in young adult white matter, it is mostly localized on oligodendrocyte cell bodies, while in aging white matter, it is also observed on myelin processes. This age-dependent re-localization and redistribution pattern mimics GluN1 expression observed during development, but in reverse order. During development, GluN1 immunoreactivity traffics from astrocytes at postnatal day 4-11 (P4-11) to myelin processes at P12-18 and to oligodendrocytes cell bodies at P19-21. Although immature axons are more resistant to ischemia, blockade of NMDA receptors during ischemia at P4-11 and P12-18 worsens axon function recovery and fails to benefit axons at P19-21. Thus, age-specific expression patterns of NMDA receptor localization may seem to modulate the plasticity of oligodendrocytes and myelin in response to ischemia as a function of age in white matter.