Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Cell Death Dis. 2013 Sep 12;4(9):e795. doi: 10.1038/cddis.2013.335.
Adult oligodendrocyte precursor cells (OPCs) are located adjacent to demyelinated lesion and contribute to myelin repair. The crucial step in remyelination is the migration of OPCs to the demyelinated area; however, the mechanism of OPC migration remains to be fully elucidated. Here we show that prostacyclin (prostaglandin I2, PGI2) promotes OPC migration, thereby promoting remyelination and functional recovery in mice after demyelination induced by injecting lysophosphatidylcholine (LPC) into the spinal cord. Prostacyclin analogs enhanced OPC migration via a protein kinase A (PKA)-dependent mechanism, and prostacyclin synthase expression was increased in the spinal cord after LPC injection. Notably, pharmacological inhibition of prostacyclin receptor (IP receptor) impaired remyelination and motor recovery, whereas the administration of a prostacyclin analog promoted remyelination and motor recovery after LPC injection. Our results suggest that prostacyclin could be a key molecule for facilitating the migration of OPCs that are essential for repairing demyelinated areas, and it may be useful in treating disorders characterized by demyelination.
成体少突胶质前体细胞（OPC）位于脱髓鞘病变附近，有助于髓鞘修复。髓鞘再生的关键步骤是 OPC 向脱髓鞘区域迁移；然而，OPC 迁移的机制仍有待充分阐明。在这里，我们发现前列环素（前列腺素 I2，PGI2）可促进 OPC 迁移，从而促进注射溶血磷脂酰胆碱（LPC）诱导的脱髓鞘后小鼠的髓鞘再生和功能恢复。前列环素类似物通过蛋白激酶 A（PKA）依赖性机制增强 OPC 迁移，并且在 LPC 注射后脊髓中表达增加。值得注意的是，前列环素受体（IP 受体）的药理学抑制会损害髓鞘再生和运动功能恢复，而前列环素类似物的给药可促进 LPC 注射后的髓鞘再生和运动功能恢复。我们的结果表明，前列环素可能是促进对修复脱髓鞘区域至关重要的 OPC 迁移的关键分子，它可能对治疗以脱髓鞘为特征的疾病有用。
