The role of SVZ-derived neural precursors in demyelinating diseases:: From animal models to multiple sclerosis
The role of SVZ-derived neural precursors in demyelinating diseases:: From animal models to multiple sclerosis
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DOI：
10.1016/j.jns.2007.09.032
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发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Baron-Van Evercooren, Anne
中科院分区：
文献类型：
--
作者：
Nait-Oumesmar, B.;Picard-Riera, Nathalle;Baron-Van Evercooren, Anne
我们将回顾内源性神经干细胞在脱髓鞘和多发性硬化症动物模型中髓磷脂修复中的作用。哺乳动物脑室下区（SVZ）是成人大脑最大的萌发区，其中包含特征明确的干细胞生态位。虽然大多数研究强调了 SVZ 祖细胞的神经源潜力，但最近的数据表明 SVZ 细胞会对不同的病理线索（如创伤、缺血、神经退行性变、炎症和脱髓鞘）做出反应。啮齿动物脱髓鞘实验模型表明，作为对脱髓鞘的反应，SVZ 祖细胞的增殖和募集到髓鞘病变中得到增强。此外，细胞谱系追踪实验表明，SVZ 祖细胞可以在脱髓鞘病变中产生少突胶质细胞，这可能有助于髓鞘再生。为了检验这些研究与髓磷脂疾病的相关性，我们最近检查了死后多发性硬化症大脑中的人类 SVZ。人类 SVZ 的特征是侧脑室室管膜边缘有一条 SVZ 星形胶质细胞带，在体外表现为多能祖细胞。我们发现，与非神经对照相比，MS SVZ 中的细胞密度和增殖有所增强。这种高细胞密度与 MS SVZ 以及心室下病变中祖细胞数量的增加相关。有趣的是，其中一些祖细胞表达参与少突胶质细胞发生的转录因子，例如 Sox9、Olig2 和 Sox10。这些数据表明，胶质细胞生成也发生在 MS SVZ 中，并表明 SVZ 衍生的少突胶质细胞前体被募集至心室周围脱髓鞘病变。对啮齿动物和非人类灵长类动物大脑中的成体神经干细胞及其祖细胞的进一步研究应有助于深入了解它们响应脱髓鞘的激活过程及其在髓磷脂修复中的作用。 (C) 2007 年由 Elsevier B.V. 出版
We will review the role of endogenous neural stem cells in myelin repair both in animal models of demyelination and multiple sclerosis. The mammalian sub-ventricular zone (SVZ) is the largest germinative zone of the adult brain, which contains a well characterized stem cell niche. While most studies highlight the neurogenic potential of SVZ progenitors, recent data indicate that SVZ cells become reactived in response to different pathological cues, like trauma, ischemia, neurodegeneration, inflammation and demyelination. Experimental models of demyelination in rodent demonstrate enhanced proliferation and recruitment of SVZ progenitors into myelin lesions, in response to demyelination. Moreover, cell lineage tracing experiments showed that SVZ progenitor cells can give rise to oligodendrocytes in demyelinated lesions, that could potentially contribute to remyelination. To examine the relevance of these studies in myelin diseases, we recently examined the human SVZ in post-mortem MS brains. The human SVZ is characterized by a ribbon of SVZ astrocytes lining the ependymal border of the lateral ventricles and which behave as multipotential progenitors in vitro. We showed that cellular density and proliferation were enhanced in MS SVZ compared to non-neurological controls. This high cellular density was correlated with the increased number of progenitor cells in MS SVZ, as well as in sub-ventricular lesions. Interestingly, some of these progenitors expressed transcription factors involved in oligodendrogenesis, such as Sox9, Olig2 and Sox10. These data indicate that gliogenesis occurs also in MS SVZ and suggest the recruitment of SVZ-derived oligodendrocyte precursors to peri-ventricular demyelinated lesions. Further investigation of adult neural stem cells and their progenitors in the brain of rodents and non-human primates should help to gain insights in their process of activation in response to demyelination and their role in myelin repair. (C) 2007 Published by Elsevier B.V.