Luo Jie, Shook Brett A, Daniels Stephen B, Conover Joanne C
Center for Regenerative Biology, Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269-4243, USA.
J Neurosci. 2008 Apr 2;28(14):3804-13. doi: 10.1523/JNEUROSCI.0224-08.2008.
The subventricular zone (SVZ) of the adult mouse brain is a narrow stem cell niche that lies along the length of the lateral wall of the lateral ventricles. The SVZ supports neurogenesis throughout adulthood; however, with increasing age, the ventral SVZ deteriorates and only the dorsolateral SVZ remains neurogenic. Associated with the elderly dorsolateral SVZ, we reported previously an increased number of astrocytes interposed within the adjacent ependymal lining. Here, we show that astrocytes integrated within the ependyma are dividing, BrdU-labeled astrocytes that share cellular adherens with neighboring ependymal cells. By tracking BrdU-labeled astrocytes over time, we observed that, as they incorporated within the ependyma, they took on antigenic and morphologic characteristics of ependymal cells, suggesting a novel form of SVZ-supported "regenerative" repair in the aging brain. A similar form of SVZ-mediated ependyma repair was also observed in young mice after mild ependymal cell denudation with low dosages of neuraminidase. Together, this work identifies a novel non-neuronal mechanism of regenerative repair by the adult SVZ.
成年小鼠脑的脑室下区(SVZ)是一个狭窄的干细胞生态位,沿侧脑室侧壁全长分布。SVZ在成年期全程支持神经发生;然而,随着年龄增长,腹侧SVZ会退化,只有背外侧SVZ仍具有神经发生能力。关于老年背外侧SVZ,我们之前报道过相邻室管膜内衬中插入的星形胶质细胞数量增加。在此,我们表明整合在室管膜内的星形胶质细胞正在分裂,即与相邻室管膜细胞共享细胞黏附结构的BrdU标记星形胶质细胞。通过长期追踪BrdU标记的星形胶质细胞,我们观察到,当它们整合到室管膜内时,会呈现出室管膜细胞的抗原和形态特征,这表明在衰老大脑中存在一种由SVZ支持的新型“再生”修复形式。在用低剂量神经氨酸酶轻度剥脱室管膜细胞后,在年轻小鼠中也观察到了类似的由SVZ介导的室管膜修复形式。总之,这项研究确定了成年SVZ进行再生修复的一种新型非神经元机制。