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首页> 外文期刊>Cell and Tissue Research >Effect of 6-hydroxydopamine (6-OHDA) on proliferation of glial cells in the rat cortex and striatum: evidence for de-differentiation of resident astrocytes.
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Effect of 6-hydroxydopamine (6-OHDA) on proliferation of glial cells in the rat cortex and striatum: evidence for de-differentiation of resident astrocytes.

机译：6-羟基多巴胺（6-OHDA）对大鼠皮质和纹状体中神经胶质细胞增殖的影响：驻留星形胶质细胞去分化的证据。

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摘要

Reactive astrogliosis is the universal response to any brain insult. It is characterized by cellular hypertrophy, up-regulation of the astrocyte marker glial fibrillary acidic protein (GFAP), and proliferation. The source of these proliferating cells is under intense debate. Progenitor cells derived from the subventricular zone (SVZ), cells positive for chondroitin sulfate proteoglycan (NG2(+)), and de-differentiated astrocytes have been proposed as the origin of proliferating cells following injury. We have analyzed the effect of intraventricular-applied 6-hydroxydopamine (6-OHDA) on the proliferation and morphology of astrocytes in rat cortex and striatum by means of immunohistochemistry and confocal laser microscopy. At 4 days post-lesion, GFAP expression increased markedly. A subpopulation of the GFAP(+) cells co-expressed Ki-67, indicating that these cells were proliferating. To investigate whether these cells (1) arose from migrating SVZ progenitor cells, (2) derived from NG2(+) progenitor cells, or (3) de-differentiated from resident astrocytes, we studied the expression of the migration marker doublecortin (Dcx), the oligodendrocyte progenitor marker NG2, and the progenitor markers Nestin and Pax6. The proliferating Ki-67(+) cells co-expressed Nestin and Pax6, whereas no co-expression of Ki-67 with NG2 or the migration marker Dcx was observed. Thus, resident astrocytes de-differentiate, in response to the intraventricular application of 6-OHDA, to a phenotype resembling radial glia cells, which represent transient astrocyte precursors during development. An understanding of the mechanisms of the de-differentiation of mature astrocytes might be useful for designing new approaches to cell therapy in neurodegenerative diseases such as Parkinson's disease.
机译：反应性星形胶质增生是对任何脑部损伤的普遍反应。它的特征是细胞肥大，星形胶质细胞标记神经胶质纤维酸性蛋白（GFAP）的上调和增殖。这些增殖细胞的来源正在激烈辩论中。已经提出了源自脑室下区域（SVZ）的祖细胞，硫酸软骨素蛋白聚糖（NG2（+））阳性的细胞以及去分化的星形胶质细胞是损伤后增殖细胞的起源。我们已经通过免疫组织化学和共聚焦激光显微镜分析了脑室内应用6-羟基多巴胺（6-OHDA）对大鼠皮质和纹状体中星形胶质细胞增殖和形态的影响。病变后4天，GFAP表达明显增加。 GFAP（+）细胞的亚群共表达Ki-67，表明这些细胞正在增殖。为了研究这些细胞（1）是否起源于迁移的SVZ祖细胞，（2）源自NG2（+）祖细胞或（3）从常驻星形胶质细胞去分化，我们研究了迁移标记物双皮质素（Dcx）的表达，少突胶质细胞祖细胞标记物NG2和祖细胞标记物Nestin和Pax6。增殖的Ki-67（+）细胞共表达Nestin和Pax6，而未观察到Ki-67与NG2或迁移标记Dcx的共表达。因此，响应于6-OHDA的脑室内应用，常驻星形胶质细胞去分化为类似于放射状神经胶质细胞的表型，其代表发育期间的瞬时星形胶质细胞前体。了解成熟的星形胶质细胞去分化的机制可能有助于设计神经退行性疾病（如帕金森氏病）中细胞治疗的新方法。

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