Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination
Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination
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DOI：
10.1111/j.1365-2990.2007.00879.x
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发表时间：
2008-02-01
影响因子：
5
通讯作者：
Stangel, M.
中科院分区：
文献类型：
--
作者：
Lindner, M.;Heine, S.;Stangel, M.
了解髓鞘再生的机制和再生失败的原因是多发性硬化症研究的主要挑战之一。这需要良好的知识和可靠的实验模型分析。这项工作是为了描述实验性髓鞘再生过程中髓鞘蛋白表达的模式。用0.3%铜酮喂养6周，诱导急性胼胝体脱髓鞘，10周后再脱髓鞘。采用Luxol快速蓝（LFB）髓磷脂染色、电镜（EM）和免疫组化相结合的方法检测髓磷脂蛋白2′，3′-环核苷酸3′磷酸二酯酶（CNPase）、髓鞘碱性蛋白（MBP）、蛋白脂质蛋白（PLP）和髓鞘少突胶质细胞糖蛋白（MOG）。早在4天通过CNPase、MBP和PLP的重新表达检测早期髓鞘再生。MOG作为少突胶质细胞晚期分化的标志，直到髓鞘再生2周才被检测到。EM数据与LFB髓磷脂染色和髓磷脂蛋白表达密切相关，50%的轴突在2周内迅速重新髓鞘化。虽然特别是MBP， PLP和CNPase在EM观察到明显的髓鞘再生之前很早就重新表达，但晚期标记MOG显示滞后于EM检测到的髓鞘再生。目前的数据表明，在髓鞘形成过程中早期和晚期表达的各种髓鞘蛋白的免疫组织化学是一种合适和可靠的方法，可以跟踪铜锌模型中的髓鞘再生。此外，对早期髓鞘再生的研究证实，内在修复程序非常快，并在几天内启动。
To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute demyelination of the corpus callosum was induced by feeding of 0.3% cuprizone for 6 weeks, followed by a 10-week remyelination period. We used a combination of Luxol fast blue (LFB) myelin staining, electron microscopy (EM) and immunohistochemistry for the myelin proteins 2 ',3 '-cyclic nucleotide 3 ' phosphodiesterase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Early remyelination was detected by the re-expression of CNPase, MBP and PLP as early as 4 days. MOG, as a marker for late differentiation of oligodendrocytes, was not detectable until 2 weeks of remyelination. EM data correlated well with the LFB myelin staining and myelin protein expression, with 50% of the axons being rapidly remyelinated within 2 weeks. While particularly MBP but also PLP and CNPase are re-expressed very early before significant remyelination is observed by EM, the late marker MOG shows a lag behind the remyelination detected by EM. The presented data indicate that immunohistochemistry for various myelin proteins expressed early and late during myelin formation is a suitable and reliable method to follow remyelination in the cuprizone model. Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days.