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皮质损伤刺激成年脑室下区神经祖细胞增殖并迁移至损伤部位。

Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury.

作者信息

Saha Bhaskar, Peron Sophie, Murray Kerren, Jaber Mohamed, Gaillard Afsaneh

机构信息

INSERM, U1084, Poitiers F-86022, France; Université de Poitiers, Poitiers F-86022, France.

出版信息

Stem Cell Res. 2013 Nov;11(3):965-77. doi: 10.1016/j.scr.2013.06.006. Epub 2013 Jun 24.

Abstract

The subventricular zone (SVZ) is the principal neurogenic niche present in the adult non-human mammalian brain. Neurons generated in the SVZ migrate along the rostral migratory stream to reach the olfactory bulb. Brain injuries stimulate SVZ neurogenesis and direct migration of new progenitors to the sites of injury. To date, cortical injury-induced adult SVZ neurogenesis in mice remains ambiguous and migration of neural progenitors to the site of injury has not been studied in detail. Here we report that aspiration lesion in the motor cortex induces a transient, but significant increase in the proliferation as well as neurogenesis in the SVZ. New neural progenitors migrate ectopically to the injured area with the assistance of blood vessels and reactive astrocytes. The SVZ origin of these progenitors was further confirmed using lentiviral transduction. In addition, we show that astrocyte-assisted ectopic migration is regulated by CXCR4/SDF-1 signaling pathway. Finally, upon reaching the lesion area, these progenitors differentiate mainly into glial cells and, to a lesser extent, mature neurons. These data provide a detailed account of the changes occurring in the SVZ and the cortex following lesion, and indicate the potential of the endogenous neural progenitors in cortical repair.

摘要

室下区(SVZ)是成年非人类哺乳动物大脑中主要的神经源性微环境。在SVZ产生的神经元沿着吻侧迁移流迁移至嗅球。脑损伤会刺激SVZ神经发生,并引导新的祖细胞直接迁移至损伤部位。迄今为止,小鼠中皮质损伤诱导的成年SVZ神经发生仍不明确,且神经祖细胞向损伤部位的迁移尚未得到详细研究。在此,我们报告运动皮质的抽吸性损伤会诱导SVZ中增殖以及神经发生出现短暂但显著的增加。新的神经祖细胞在血管和反应性星形胶质细胞的协助下异位迁移至损伤区域。使用慢病毒转导进一步证实了这些祖细胞的SVZ起源。此外,我们表明星形胶质细胞辅助的异位迁移受CXCR4/SDF-1信号通路调控。最后,到达损伤区域后,这些祖细胞主要分化为胶质细胞,在较小程度上分化为成熟神经元。这些数据详细描述了损伤后SVZ和皮质中发生的变化,并表明内源性神经祖细胞在皮质修复中的潜力。

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