Vana Adam C, Lucchinetti Claudia F, Le Tuan Q, Armstrong Regina C
Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Glia. 2007 May;55(7):687-97. doi: 10.1002/glia.20492.
Myelin transcription factor 1 (Myt1) is a zinc-finger DNA binding protein that influences developing oligodendrocyte progenitor (OP) cell proliferation, differentiation, and myelin gene transcription in vitro. The potential of Myt1 to play a role in OP responses leading to remyelination was examined using murine hepatitis virus strain A59 (MHV) to induce spinal cord demyelination and potential relevance to human pathology was evaluated in multiple sclerosis (MS) lesions. In MHV-infected mice, the density of Myt1 expressing cells markedly increased in lesioned areas of spinal cord white matter. Myt1 expressing cells proliferated most extensively during active demyelination and subsequently accumulated to maximal levels during early remyelination. Cells with nuclear Myt1 immunoreactivity were mainly OP cells, identified by co-localization with platelet-derived growth factor alpha receptor, with additional phenotypes being either oligodendrocytes or neural stem cells, identified by CC1 antigen and Musashi1, respectively. The density of OP cells expressing Myt1 was significantly increased in white matter of MHV-infected mice during demyelination and early remyelination then as remyelination advanced the values returned to levels comparable to PBS-injected control mice. In MHV lesions, Myt1 was not expressed in astrocytes, lymphocytes, or macrophage/microglial cells. MS lesions demonstrated increased Myt1 expression in both the periplaque white matter adjacent to lesions and within early remyelinating lesions. These results suggesta potential role for Myt1 in the regeneration of oligodendrocyte lineage cells in response to demyelination.
髓鞘转录因子1（Myt1）是一种锌指DNA结合蛋白，在体外可影响少突胶质前体细胞（OP）的增殖、分化及髓鞘基因转录。利用A59株鼠肝炎病毒（MHV）诱导脊髓脱髓鞘，研究了Myt1在导致髓鞘再生的OP反应中发挥作用的可能性，并在多发性硬化症（MS）病变中评估了其与人类病理学的潜在相关性。在感染MHV的小鼠中，脊髓白质病变区域中表达Myt1的细胞密度显著增加。在活跃脱髓鞘期间，表达Myt1的细胞增殖最为广泛，随后在早期髓鞘再生期间积累至最高水平。细胞核Myt1免疫反应阳性的细胞主要是OP细胞，通过与血小板衍生生长因子α受体共定位来鉴定，另外的表型分别是少突胶质细胞或神经干细胞，通过CC1抗原和Musashi1来鉴定。在脱髓鞘和早期髓鞘再生期间，感染MHV的小鼠白质中表达Myt1的OP细胞密度显著增加，然后随着髓鞘再生的推进，其值恢复到与注射PBS的对照小鼠相当的水平。在MHV病变中，星形胶质细胞、淋巴细胞或巨噬细胞/小胶质细胞中不表达Myt1。MS病变显示，病变周围白质和早期髓鞘再生病变中Myt1表达均增加。这些结果表明，Myt1在少突胶质细胞谱系细胞对脱髓鞘反应的再生中可能发挥作用。
