Macroglial plasticity and the origins of reactive astroglia in experimental autoimmune encephalomyelitis.
Macroglial plasticity and the origins of reactive astroglia in experimental autoimmune encephalomyelitis.
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DOI：
10.1523/jneurosci.1759-11.2011
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发表时间：
2011-08-17
期刊：
影响因子：
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通讯作者：
Pleasure D
中科院分区：
文献类型：
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作者：
Guo F;Maeda Y;Ma J;Delgado M;Sohn J;Miers L;Ko EM;Bannerman P;Xu J;Wang Y;Zhou C;Takebayashi H;Pleasure D
肥大的、强胶质细胞酸性蛋白阳性（GFAP）+星形胶质细胞的积累，其也表达免疫反应性巢蛋白和波形蛋白，是多发性硬化病变的突出特征。肥大性GFAP+/波形蛋白+/巢蛋白+“反应性”星形胶质细胞的细胞起源问题以及多发性硬化症和其他CNS疾病期间三种大胶质细胞祖细胞群体-少突胶质细胞祖细胞（OPCs）、星形胶质细胞和室管膜细胞-之间的可塑性和谱系关系仍然存在争议。我们采用一组诱导型Cre驱动因子（Olig 2-Cre-ERT 2，GFAP-Cre-ERT 2，FoxJ 1-Cre-ERT 2和Nestin-Cre-ERT 2）的遗传命运映射来探索患有髓鞘少突胶质细胞糖蛋白肽诱导的实验性自身免疫性脑脊髓炎（EAE）的成年小鼠中的这些问题。脊髓OPCs的增殖率上升5倍以上的控制水平，在EAE，少突胶质细胞的数量增加，以及，但从OPCs的星形细胞是罕见的。脊髓室管膜细胞，以前报道是多能的，没有增加其低增殖率，也没有引起星形胶质细胞或OPCs。相反，在该多发性硬化模型中，在脊髓中积累的肥大的、波形蛋白+/巢蛋白+、反应性星形胶质细胞是通过白色物质中的纤维性星形胶质细胞的增殖和表型转化衍生的，并且仅通过灰质中的原生质性星形胶质细胞的表型转化衍生的。EAE中大胶质细胞可塑性的综合分析有助于阐明CNS炎性脱髓鞘疾病中星形胶质细胞增生的起源。
Accumulations of hypertrophic, intensely glial fibrillary acidic protein positive (GFAP)+ astroglia, which also express immunoreactive nestin and vimentin, are prominent features of multiple sclerosis lesions. The issues of the cellular origin of hypertrophic GFAP+/vimentin+/nestin+ “reactive” astroglia and also the plasticities and lineage relationships among three macroglial progenitor populations - oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal cells - during multiple sclerosis and other CNS diseases remain controversial. We employed genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre-ERT2, GFAP-Cre-ERT2, FoxJ1-Cre-ERT2 and Nestin-Cre-ERT2) to explore these issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis (EAE). The proliferative rate of spinal cord OPCs rose five-fold above control levels during EAE, and numbers of oligodendroglia increased as well, but astrogenesis from OPCs was rare. Spinal cord ependymal cells, previously reported to be multipotent, did not augment their low proliferative rate, nor give rise to astroglia or OPCs. Instead, the hypertrophic, vimentin+/nestin+, reactive astroglia that accumulated in spinal cord in this multiple sclerosis model were derived by proliferation and phenotypic transformation of fibrous astroglia in white matter, and solely by phenotypic transformation of protoplasmic astroglia in gray matter. This comprehensive analysis of macroglial plasticity in EAE helps to clarify the origins of astrogliosis in CNS inflammatory demyelinative disorders.