Hattiangady Bharathi, Shetty Ashok K
Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC 27710, United States.
Neurobiol Aging. 2008 Jan;29(1):129-47. doi: 10.1016/j.neurobiolaging.2006.09.015. Epub 2006 Nov 7.
To investigate whether dramatically waned dentate neurogenesis during aging is linked to diminution in neural stem/progenitor cell (NSC) number, we counted cells immunopositive for Sox-2 (a putative marker of NSCs) in the subgranular zone (SGZ) of young, middle-aged and aged F344 rats. The young SGZ comprised approximately 50,000 Sox-2+ cells and this amount did not diminish with aging. Quantity of GFAP+ cells and vimentin+ radial glia also remained stable during aging in this region. Besides, in all age groups, analogous fractions of Sox-2+ cells expressed GFAP (astrocytes/NSCs), NG-2 (oligodendrocyte-progenitors/NSCs), vimentin (radial glia), S-100beta (astrocytes) and doublecortin (new neurons). Nevertheless, analyses of Sox-2+ cells with proliferative markers insinuated an increased quiescence of NSCs with aging. Moreover, the volume of rat-endothelial-cell-antigen-1+ capillaries (vascular-niches) within the SGZ exhibited an age-related decline, resulting in an increased expanse between NSCs and capillaries. Thus, decreased dentate neurogenesis during aging is not attributable to altered number or phenotype of NSCs. Instead, it appears to be an outcome of increased quiescence of NSCs due to changes in NSC milieu.
为了研究衰老过程中齿状回神经发生显著减少是否与神经干细胞/祖细胞(NSC)数量的减少有关,我们对年轻、中年和老年F344大鼠齿状回颗粒下区(SGZ)中Sox-2(一种假定的NSC标志物)免疫阳性的细胞进行了计数。年轻大鼠的SGZ中约有50,000个Sox-2+细胞,且这一数量并未随衰老而减少。该区域中GFAP+细胞和波形蛋白+放射状胶质细胞的数量在衰老过程中也保持稳定。此外,在所有年龄组中,Sox-2+细胞中表达GFAP(星形胶质细胞/NSC)、NG-2(少突胶质细胞前体细胞/NSC)、波形蛋白(放射状胶质细胞)、S-100β(星形胶质细胞)和双皮质素(新神经元)的比例相似。然而,对具有增殖标志物的Sox-2+细胞的分析表明,随着衰老,NSC的静止状态增加。此外,SGZ内大鼠内皮细胞抗原-1+毛细血管(血管微环境)的体积呈现与年龄相关的下降,导致NSC与毛细血管之间的距离增加。因此,衰老过程中齿状回神经发生减少并非归因于NSC数量或表型的改变。相反,它似乎是由于NSC微环境变化导致NSC静止状态增加的结果。