The aging neurogenic subventricular zone
The aging neurogenic subventricular zone
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DOI：
10.1111/j.1474-9726.2006.00197.x
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发表时间：
2006-04-01
期刊：
影响因子：
7.8
通讯作者：
Conover, JC
中科院分区：
文献类型：
--
作者：
Luo, J;Daniels, SB;Conover, JC
在成年小鼠大脑中，脑室下区（SVZ）是一个只有4-5个细胞直径厚的神经源性干细胞生态位。在这个狭窄的区域内，一个独特的微环境支持干细胞自我更新、胶质细胞形成或神经发生谱系的决定，以及新生成的神经元从SVZ向嗅球的切向迁移。然而，随着年龄的增长，SVZ神经发生减少。在这里，我们通过衰老研究SVZ细胞结构和神经发生之间的动态相互作用。将2个月、10个月和22个月大的小鼠相应冠状切片的高分辨率电子显微镜图像组装成合成照片，显示SVZ随着年龄的增长而变薄。在2小时BrdU脉冲后，我们检测到细胞增殖从2到22个月显著下降。神经母细胞数量随着年龄的增长而减少，短暂性扩增祖细胞也是如此，而SVZ星形胶质细胞和邻近的室管膜细胞保持相对恒定。在22个月时，只剩下残余的神经发生袋，神经母细胞被限制在SVZ的前背外侧角。在这个背外侧区域内，年轻神经源性生态位的许多关键成分得以维持；然而，在老年SVZ中，室管膜内发现SVZ星形胶质细胞数量增加。这些星形胶质细胞与室管膜细胞和星形胶质细胞的标记物共同标记，与邻近的室管膜细胞形成细胞间粘附连接，有些在其细胞质内具有多个纤毛基体。综上所述，这些数据表明，随着室管膜内SVZ星形胶质细胞数量的增加，SVZ神经发生在侧脑室背外侧的进行性限制与年龄相关。
In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 cell diameters thick. Within this narrow zone, a unique microenvironment supports stem cell self-renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out of the SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines. Here, we examine the dynamic interplay between SVZ cytoarchitecture and neurogenesis through aging. Assembly of high-resolution electron microscopy images of corresponding coronal sections from 2-, 10- and 22-month-old mice into photomontages reveal a thinning of the SVZ with age. Following a 2-h BrdU pulse, we detect a significant decrease in cell proliferation from 2 to 22 months. Neuroblast numbers decrease with age, as do transitory amplifying progenitor cells, while both SVZ astrocytes and adjacent ependymal cells remain relatively constant. At 22 months, only residual pockets of neurogenesis remain and neuroblasts become restricted to the anterior dorsolateral horn of the SVZ. Within this dorsolateral zone many key components of the younger neurogenic niche are maintained; however, in the aged SVZ, increased numbers of SVZ astrocytes are found interposed within the ependyma. These astrocytes co-label with markers to ependymal cells and astrocytes, form intercellular adherens junctions with neighboring ependymal cells, and some possess multiple basal bodies of cilia within their cytoplasm. Together, these data reveal an age-related, progressive restriction of SVZ neurogenesis to the dorsolateral aspect of the lateral ventricle with increased numbers of SVZ astrocytes interpolated within the ependyma.