In vivo proliferation of oligodendrocyte progenitors expressing PDGFalphaR during early remyelination.
In vivo proliferation of oligodendrocyte progenitors expressing PDGFalphaR during early remyelination.
复制标题
DOI：
10.1002/(sici)1097-4695(19981115)37:3
复制
发表时间：
1998-11
期刊：
影响因子：
--
通讯作者：
J. Redwine;R. Armstrong
中科院分区：
文献类型：
--
作者：
J. Redwine;R. Armstrong
内源性少突胶质细胞系细胞自发地使C57 Bl/6小鼠的鼠肝炎病毒A59感染诱导的脱髓鞘局灶性区域重新髓鞘化。我们使用该模型来研究血小板源性生长因子（PDGF）在重新填充脱髓鞘病变中发挥作用的潜力，并且在此过程中，我们还进一步表征了脱髓鞘后少突胶质细胞谱系细胞的体内反应。在髓鞘再生过程的早期，我们给予4小时的溴脱氧尿苷（BrdU）体内脉冲，随后进行原位杂交的PDGF-α受体（PDGFalphaR），一个既定的标记少突胶质细胞祖细胞在体内，或蛋白脂质蛋白（PLP），以确定少突胶质细胞。损伤脊髓切片中BrdU标记的少突胶质细胞祖细胞（PDGFalphaR+）的数量增加了14.5倍，而BrdU标记的少突胶质细胞（PLP+）非常罕见。相似切片的免疫细胞化学显示，PDGFalphaR和NG 2（少突胶质细胞祖细胞的另一种标志物）的免疫反应性在白质病变区域局部增加。高分辨率免疫荧光成像用于检测表达PDGF和成纤维细胞生长因子受体的少突胶质细胞祖细胞。此外，PDGF-A mRNA转录本的表达在受损脊髓的切片中增加，并且病变中的反应性星形胶质细胞表现出对PDGF配体的免疫反应性。我们的研究结果表明，在髓鞘再生的初始阶段，少突胶质细胞祖细胞局部增殖，这种反应可能涉及PDGF。
Endogenous oligodendrocyte lineage cells spontaneously remyelinate focal areas of demyelination induced by murine hepatitis virus A59 infection of C57Bl/6 mice. We used this model to examine the potential for platelet-derived growth factor (PDGF) to have a role in repopulating demyelinated lesions, and in doing so we also further characterized the in vivo responses of oligodendrocyte lineage cells following demyelination. Very early in the progress of remyelination, we administered a 4-h in vivo pulse of bromodeoxyuridine (BrdU) and subsequently performed in situ hybridization for PDGF-alpha receptor (PDGFalphaR), an established marker for oligodendrocyte progenitors in vivo, or for proteolipid protein (PLP), to identify oligodendrocytes. Sections of lesioned spinal cords had a 14.5-fold increase in the number of BrdU-labeled oligodendrocyte progenitor cells (PDGFalphaR+), while BrdU-labeled oligodendrocytes (PLP+) were extremely rare. Immunocytochemistry of similar sections demonstrated that immunoreactivity for both PDGFalphaR and NG2, another marker of oligodendrocyte progenitors, was locally increased in areas of white-matter lesions. High-resolution immunofluorescence imaging was used to detect oligodendrocyte progenitor cells expressing receptors for both PDGF and fibroblast growth factor. In addition, expression of PDGF-A mRNA transcripts was increased in sections of lesioned spinal cords and reactive astrocytes in lesions exhibited immunoreactivity for PDGF ligand. Our findings indicate that during the initial stages of remyelination, oligodendrocyte progenitors proliferate locally, and that this response may potentially involve PDGF.