Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois, USA.
Glia. 2011 Jun;59(6):914-26. doi: 10.1002/glia.21163. Epub 2011 Mar 28.
Myelin repair is inhibited in multiple sclerosis (MS), ultimately leading to axonal damage and disability. We aimed to understand the transcriptional mechanisms of regeneration in primary human oligodendrocyte cultures isolated from white matter of medically intractable epilepsy patients. Cultures at isolation contained 84% mature oligodendrocytes and 16% oligodendrocyte progenitor cells (OPC). The two populations showed a protracted regeneration of membranes expressing myelin proteins after 2-3 weeks in culture, and were kept long-term to study membranes maintenance. We profiled by quantitative PCR (qPCR) the sequential mRNA expression of transcription factors Olig1, Olig2, Nkx2.2, Sox10, PPARδ, PPARγ, cyclic nucleotide phosphodiesterase (CNP), myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG). In summary, Olig1 was not expressed in freshly isolated oligodendrocytes, but was expressed from the beginning of process extension until membranes maintenance. In contrast, Olig2 expression was restricted to isolation and during membranes production. We show for the first time PPARδ expression and absence of PPARγ in human oligodendrocytes. Nkx2.2, Sox10, PPARδ, CNP, MBP and MOG messengers were expressed at any time, while MAG messenger was expressed at mature stage only. Myelin proteins CNP, MBP, MAG, and MOG were confirmed by immunocytochemistry. Our findings point to different roles of Olig1 and Olig2 in regeneration of cultured adult human oligodendrocytes. Noticeably, the transcriptional profiles found in cultured neonatal rodent OPC are different. More studies are necessary to elucidate myelin repair in the adult human brain.
髓鞘修复在多发性硬化症（MS）中受到抑制，最终导致轴突损伤和残疾。我们的目的是了解从医学上无法治疗的癫痫患者的白质中分离的原代人少突胶质细胞培养物中的再生转录机制。培养物在分离时包含 84%的成熟少突胶质细胞和 16%的少突胶质前体细胞（OPC）。这两个群体在培养 2-3 周后表现出髓鞘蛋白表达的膜再生延长，并且被长期保留以研究膜维持。我们通过定量 PCR（qPCR）对转录因子 Olig1、Olig2、Nkx2.2、Sox10、PPARδ、PPARγ、环核苷酸磷酸二酯酶（CNP）、髓鞘碱性蛋白（MBP）、髓鞘相关糖蛋白（MAG）和髓鞘少突胶质糖蛋白（MOG）的顺序 mRNA 表达进行了分析。总的来说，Olig1 在新鲜分离的少突胶质细胞中不表达，但从开始延伸过程到维持膜时表达。相比之下，Olig2 的表达仅限于分离和膜生成期间。我们首次在人少突胶质细胞中显示出 PPARδ 的表达和缺乏 PPARγ。Nkx2.2、Sox10、PPARδ、CNP、MBP 和 MOG 信使在任何时候都表达，而 MAG 信使仅在成熟阶段表达。免疫细胞化学证实了髓鞘蛋白 CNP、MBP、MAG 和 MOG 的表达。我们的发现表明 Olig1 和 Olig2 在培养的成人人类少突胶质细胞再生中具有不同的作用。值得注意的是，在培养的新生啮齿动物 OPC 中发现的转录谱不同。需要更多的研究来阐明成人大脑中的髓鞘修复。
