Sim F J, Hinks G L, Franklin R J
Department of Anatomy, University of Cambridge, Downing Street, CB2 3DY, Cambridge, UK.
Neuroscience. 2000;100(1):131-9. doi: 10.1016/s0306-4522(00)00252-9.
Since myelination and remyelination both involve investing an axon with a myelin sheath, a plausible hypothesis is that the two processes involve the expression of similar transcription factors. In this study we have addressed this hypothesis by comparing the expression of messenger RNA of Gtx, a homeodomain transcription factor expressed within oligodendrocytes during myelination, with the expression of messenger RNAs of the major myelin proteins, myelin basic protein and proteolipid protein during remyelination of experimentally induced demyelination in the adult rat brain. We have found a close temporal and spatial association between the expression patterns of the three messenger RNA species during remyelination. By comparing the expression patterns in rapidly remyelinating lesions in young adult rats with slowly remyelinating lesions in old adult rats, we have shown that Gtx messenger RNA expression follows the reappearance of myelin basic protein and proteolipid protein messenger RNAs regardless of the rate of remyelination. This observation demonstrates a clear association between the expression of Gtx messenger RNA and myelin repair. We have also shown that there is a decrease in constitutive levels of expression of myelin basic protein, proteolipid protein and Gtx messenger RNA in old adults compared with young adults. Taken together, our results indicate that Gtx, which has multiple binding sites in the promoter regions of both myelin basic protein and proteolipid protein genes, may have a similar role in the regulation of myelin protein gene expression during remyelination as has been proposed in myelination.
由于髓鞘形成和髓鞘再生都涉及用髓鞘包裹轴突，一个合理的假设是这两个过程涉及相似转录因子的表达。在本研究中，我们通过比较Gtx（一种在髓鞘形成过程中在少突胶质细胞内表达的同源结构域转录因子）的信使核糖核酸（mRNA）表达与成年大鼠脑实验性诱导脱髓鞘后的髓鞘再生过程中主要髓鞘蛋白（髓鞘碱性蛋白和蛋白脂蛋白）的mRNA表达，来验证这一假设。我们发现在髓鞘再生过程中，这三种mRNA的表达模式在时间和空间上密切相关。通过比较年轻成年大鼠快速髓鞘再生损伤与老年成年大鼠缓慢髓鞘再生损伤中的表达模式，我们发现无论髓鞘再生速度如何，Gtx mRNA表达都跟随髓鞘碱性蛋白和蛋白脂蛋白mRNA的重新出现。这一观察结果表明Gtx mRNA表达与髓鞘修复之间存在明显关联。我们还表明，与年轻成年大鼠相比，老年成年大鼠中髓鞘碱性蛋白、蛋白脂蛋白和Gtx mRNA的组成性表达水平有所下降。综上所述，我们的结果表明，在髓鞘碱性蛋白和蛋白脂蛋白基因启动子区域具有多个结合位点的Gtx，在髓鞘再生过程中对髓鞘蛋白基因表达的调控作用可能与髓鞘形成过程中所提出的作用类似。
