Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice
Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice
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DOI：
10.1523/jneurosci.4608-03.2004
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发表时间：
2004-02-18
影响因子：
5.3
通讯作者：
Pruitt, SC
中科院分区：
文献类型：
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作者：
Maslov, AY;Barone, TA;Pruitt, SC
哺乳动物的大脑中含有神经干细胞（NSC），可以在动物的整个生命周期中持续进行神经发生。然而，已知神经发生在衰老期间下降，并且在神经发生是正常CNS功能所需的程度上，这可能导致神经退行性疾病。神经发生的减少可能是由于神经干细胞的丢失或后期功能障碍造成的，区分这些可能性对于理解神经发生减少的原因很重要。然而，由于无法区分神经干细胞从他们的快速分裂的后代在原位，它一直是不可能的定量评估的NSC种群在年轻和年老的动物。在这份报告中，我们表明，G1期特异性表达的复制因子Mcm 2是一个有用的标志物，用于检测缓慢循环假定的神经干细胞原位和确认这些细胞的身份使用胞嘧啶β-D-阿拉伯呋喃糖苷（Ara-C）治疗和双核苷类似物标记技术。区分NSC与增殖祖细胞的能力已经允许表征这些不同细胞类型中的几种标记物（包括巢蛋白、Musashi和GFAP）的表达。此外，年轻（2-4个月）和老年（2-4 -26个月）小鼠脑室下区的NSC群体的比较表明，老年小鼠中的NSC群体减少了约两倍。在培养物中从老年动物中回收的神经球数量也观察到相对于年轻动物的类似两倍减少。这里记录的神经干细胞数量的减少足以解释老年动物神经发生水平的降低。
The mammalian brain contains neural stem cells (NSCs) that allow continued neurogenesis throughout the life of the animal. However, neurogenesis is known to decline during aging and, to the extent that neurogenesis is required for normal CNS function, this may contribute to neurodegenerative disease. Decreased neurogenesis could result from loss of NSCs or dysfunction at some later step, and distinguishing these possibilities is important for understanding the cause of the decline. However, because of the inability to distinguish NSCs from their rapidly dividing progeny in situ, it has not been possible to quantitatively assess the NSC populations in young and old animals. In this report we show that the G1 phase-specific expression of the replication factor Mcm2 is a useful marker for detecting slowly cycling putative NSCs in situ and confirm the identity of these cells using both cytosine beta-D-arabinofuranoside (Ara-C) treatment and a double nucleoside analog-labeling technique. The ability to distinguish NSCs from proliferative progenitors has allowed characterization of the expression of several markers including Nestin, Musashi, and GFAP in these different cell types. Furthermore, comparison of the NSC populations in the subventricular zones of young (2-4 months) and old (24-26 months) mice demonstrates an approximately twofold reduction in the older mice. A similar twofold reduction is also observed in the number of neurospheres recovered in culture from old relative to young animals. The reduction in the neural stem cell population documented here is sufficient to account for the reduced level of neurogenesis in old animals.