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[原稿]
类视黄醇X受体γ信号促进中枢神经系统髓鞘再生
目前对中枢神经系统髓鞘再生的分子基础的了解很少。我们获得了大鼠中枢神经系统局灶性脱髓鞘后自发性髓鞘再生各阶段的全面转录谱，结果发现，在髓鞘再生期间，编码类视黄醇受体RXR－γ的转录物存在差异表达。在有髓鞘再生的大鼠组织以及活动性的有髓鞘再生的多发性硬化病变中，少突胶质谱系细胞能够表达RXR－γ。通过RNA干扰或RXR特异的拮抗剂敲除RXR－γ严重抑制了培养物中的少突胶质细胞分化。在没有RXR－γ的小鼠中，在脱髓鞘之后，成熟少突胶质前体细胞有效地修复了病变，但延迟分化为成熟少突胶质细胞。向脱髓鞘的小脑切片培养物和脱髓鞘后的衰老大鼠给予RXR激动剂9－顺式－视黄酸能够增加轴突髓鞘再生。我们的结果表明：RXR－γ是内源性少突胶质前体细胞分化和髓鞘再生的正性调节物，并且可能是中枢神经系统再生疗法的药理学作用靶的。
[译文]
Retinoid X receptor gamma signaling accelerates CNS remyelination
The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-g were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-g in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-g by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-g, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-g is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.
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