In vivo proliferation of oligodendrocyte progenitors expressing PDGFαR during early remyelination

In vivo proliferation of oligodendrocyte progenitors expressing PDGFαR during early remyelination
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DOI:
10.1002/(sici)1097-4695(19981115)37:3
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发表时间:
1998-11-15
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
Armstrong, RC
Armstrong, RC
中科院分区:
其他
文献类型:
--
作者:
Redwine, JM;Armstrong, RC

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内源性少突胶质细胞谱系细胞自发地对 C57B1/6 小鼠的鼠肝炎病毒 A59 感染诱导的脱髓鞘病灶进行髓鞘再生。我们使用该模型来检查血小板源性生长因子(PDGF)在脱髓鞘病变再生中发挥作用的潜力,在此过程中,我们还进一步表征了脱髓鞘后少突胶质细胞系细胞的体内反应。在髓鞘再生过程的早期,我们给予了溴脱氧尿苷(BrdU)4小时体内脉冲,随后对PDGF-α受体(PDGF α R)进行了原位杂交,建立了体内少突胶质细胞祖细胞或蛋白脂质蛋白(PLP)的标记,以识别少突胶质细胞。病变脊髓切片中 BrdU 标记的少突胶质祖细胞 (PDGF α R+) 数量增加了 14.5 倍,而 BrdU 标记的少突胶质细胞 (PLP+) 极其罕见。类似切片的免疫细胞化学表明,PDGF α R 和 NG2(少突胶质细胞祖细胞的另一种标记物)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,受损脊髓切片中 PDGF-A mRNA 转录物的表达增加,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,并且这种反应可能涉及 PDGF,(C) 1998 John Wiley & Sons, Inc.*
Endogenous oligodendrocyte lineage cells spontaneously remyelinate focal areas of demyelination induced by murine hepatitis virus A59 infection of C57B1/6 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 iii vivo pulse of bromodeoxyuridine (BrdU) and subsequently performed iii situ hybridization for PDGF-alpha receptor (PDGF alpha R), 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 (PDGF alpha R+), while BrdU-labeled oligodendrocytes (PLP+) were extremely rare. Immunocytochemistry of similar sections demonstrated that immunoreactivity for both PDGF alpha R 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, (C) 1998 John Wiley & Sons, Inc.*