Luo Jie, Daniels Stephen B, Lennington Jessica B, Notti Ryan Q, Conover Joanne C
Center for Regenerative Biology, Department of Physiology and Neurobiology, University of Connecticut, Storrs, 06250-4243, USA.
Aging Cell. 2006 Apr;5(2):139-52. doi: 10.1111/j.1474-9726.2006.00197.x.
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.
在成年小鼠大脑中，脑室下区（SVZ）是一个仅4 - 5个细胞直径厚的神经源性干细胞微环境。在这个狭窄区域内，独特的微环境支持干细胞自我更新、胶质细胞生成或神经生成谱系决定，以及新生成神经元从SVZ向嗅球的切向迁移。然而，随着年龄增长，SVZ神经发生减少。在这里，我们通过衰老过程研究SVZ细胞结构与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拼接成照片蒙太奇，显示SVZ随年龄变薄。在进行2小时的溴脱氧尿苷（BrdU）脉冲标记后，我们检测到从2个月到22个月细胞增殖显著下降。神经母细胞数量随年龄减少，短暂扩增祖细胞数量也减少，而SVZ星形胶质细胞和相邻的室管膜细胞数量保持相对恒定。在22个月时，仅残留少量神经发生区域，神经母细胞局限于SVZ的前背外侧角。在这个背外侧区域，年轻神经发生微环境的许多关键成分得以保留；然而，在衰老的SVZ中，发现室管膜内插入的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，与相邻的室管膜细胞形成细胞间黏附连接，并且一些在其细胞质内具有多个纤毛基体。总之，这些数据揭示了与年龄相关的、SVZ神经发生逐渐局限于侧脑室背外侧方面的现象，同时室管膜内插入的SVZ星形胶质细胞数量增加。
