The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation
The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation
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DOI：
10.1523/jneurosci.22-07-02451.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Franklin, RJM
中科院分区：
文献类型：
--
作者：
Sim, FJ;Zhao, C;Franklin, RJM
与年龄相关的中枢神经系统髓鞘再生效率下降，对于可能持续数十年的多发性硬化症（MS）等脱髓鞘疾病的恢复具有明显的影响。制定扭转与年龄相关的衰退的策略需要确定再生过程是如何受损的。我们探讨了髓鞘再生变慢是否是因为少突胶质细胞祖细胞 (OP) 募集受损，或者如某些 MS 病变中的情况，是因为 OP 分化为髓鞘再生少突胶质细胞受损。通过原位杂交，使用探针对两种 OP 表达的 mRNA 种类：血小板源性生长因子-α 受体和 OP 转录因子髓磷脂转录因子 1 (MyT1)，比较年轻和年老大鼠局部毒素诱导的中枢神经系统脱髓鞘髓鞘再生过程中 OP 的反应。我们发现，两种 OP 标记的表达模式非常相似，表明与年轻动物相比，老年动物中 OP 的脱髓鞘病灶定植延迟。通过比较 MyT1 与髓磷脂蛋白髓磷脂碱性蛋白和 Gtx 的 mRNA 表达模式，我们发现在年老动物中，OP 分化也存在延迟，这种延迟随着生存时间的延长而增加。这些结果表明，与年龄相关的髓鞘再生效率下降是由于OP招募和随后OP分化为髓鞘再生少突胶质细胞的受损而发生的，因此，旨在改善与年龄相关的髓鞘再生效率下降的策略将需要促进再生过程的两个组成部分。
The age-associated decrease in the efficiency of CNS remyelination has clear implications for recovery from demyelinating diseases such as multiple sclerosis (MS) that may last for several decades. Developing strategies to reverse the age-associated decline requires the identification of how the regenerative process is impaired. We addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, as is the case in some MS lesions, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin-induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to two OP-expressed mRNA species: platelet-derived growth factor-alpha receptor and the OP transcription factor myelin transcription factor 1 (MyT1). We found that the expression patterns for the two OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared with the young animals. By comparing the mRNA expression pattern of MyT1 with that of the myelin proteins myelin basic protein and Gtx, we found that in the old animals there is also a delay in OP differentiation that increases with longer survival times. These results indicate that the age-associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and the subsequent differentiation of the OPs into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age-associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process.