Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation
Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation
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DOI：
10.1371/journal.pone.0076048
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发表时间：
2013-09-30
期刊：
影响因子：
3.7
通讯作者：
Van Vliet, Krystyn J.
中科院分区：
文献类型：
--
作者：
Jagielska, Anna;Wilhite, Kristen D.;Van Vliet, Krystyn J.
中枢神经系统轴突的髓鞘再生需要产生髓磷脂的少突胶质细胞。这种修复过程的失败是多发性硬化症等脱髓鞘疾病中神经退行性变的特征，目前尚不清楚病变微环境如何导致少突胶质细胞脱髓鞘潜能降低。在这里，我们发现酸性的细胞外pH值（脱髓鞘病变的特征）降低了少突胶质细胞前体细胞（OPCs）的迁移、增殖和存活，并减少了它们向少突胶质细胞的分化。此外，OPC沿着pH梯度向酸性pH方向定向迁移。这些体外研究结果支持了一种可能的体内情况，即pH梯度将OPC吸引到酸性病变，但导致OPC在酸性中的存活和运动减少，从而减少了向脱髓鞘轴突的进展，并进一步减少了向产生髓磷脂的少突胶质细胞的分化。由于这些过程是OPC对神经脱髓鞘反应的组成部分，我们的研究结果表明，病变酸度可能有助于减少髓鞘再生。
Axon remyelination in the central nervous system requires oligodendrocytes that produce myelin. Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. Here, we show that acidic extracellular pH, which is characteristic of demyelinating lesions, decreases the migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs), and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit directional migration along pH gradients toward acidic pH. These in vitro findings support a possible in vivo scenario whereby pH gradients attract OPCs toward acidic lesions, but resulting reduction in OPC survival and motility in acid decreases progress toward demyelinated axons and is further compounded by decreased differentiation into myelin-producing oligodendrocytes. As these processes are integral to OPC response to nerve demyelination, our results suggest that lesion acidity could contribute to decreased remyelination.