Adult neurogenesis in the short-lived teleost Nothobranchius furzeri: localization of neurogenic niches, molecular characterization and effects of aging.
Adult neurogenesis in the short-lived teleost Nothobranchius furzeri: localization of neurogenic niches, molecular characterization and effects of aging.
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DOI：
10.1111/j.1474-9726.2011.00781.x
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发表时间：
2012-04
期刊：
影响因子：
7.8
通讯作者：
Cellerino A
中科院分区：
文献类型：
--
作者：
Tozzini ET;Baumgart M;Battistoni G;Cellerino A
我们研究了成年神经发生在短命的一年生鱼Nothobranchius furzeri和量化的有丝分裂活动的神经元祖细胞和神经胶质细胞酸性蛋白（GFAP）在放射状胶质细胞的表达老化的影响。神经原性小生境的分布与斑马鱼基本相似，成体干细胞产生神经元，这些神经元在成体大脑中持续存在。然而，与斑马鱼相反，N. furzeri基因组含有双皮质素（DCX）基因。Doublecortin由端脑和视顶盖（OT）中新产生的神经元瞬时表达。我们还分析了microRNA miR-9和miR-124的表达，发现它们具有互补的表达结构域：miR-9在端脑和OT放射状胶质细胞的神经原性小生境中表达，而miR-124在分化的神经元中表达。本文的主要发现是成年神经发生的年龄依赖性衰减的示范。使用无偏的体视学估计的细胞数量，我们检测到一个几乎五倍的减少有丝分裂活跃的细胞在OT之间的年轻和老年。这种减少的有丝分裂活性被DCX标记的减少所掩盖。最后，我们检测到一个戏剧性的上调GFAP在放射状胶质细胞的老年大脑。这种上调并不被S100 B和Musashi-1（放射状胶质细胞的另外两个标志物）的类似上调所掩盖。综上所述，N. furzeri复制了哺乳动物衰老的两个典型标志：神经胶质增生和成年神经发生减少。
We studied adult neurogenesis in the short-lived annual fish Nothobranchius furzeri and quantified the effects of aging on the mitotic activity of the neuronal progenitors and the expression of glial fibrillary acid protein (GFAP) in the radial glia. The distribution of neurogenic niches is substantially similar to that of zebrafish and adult stem cells generate neurons, which persist in the adult brain. As opposed to zebrafish, however, the N. furzeri genome contains a doublecortin (DCX) gene. Doublecortin is transiently expressed by newly generated neurons in the telencephalon and optic tectum (OT). We also analyzed the expression of the microRNA miR-9 and miR-124 and found that they have complementary expression domains: miR-9 is expressed in the neurogenic niches of the telencephalon and the radial glia of the OT, while miR-124 is expressed in differentiated neurons. The main finding of this paper is the demonstration of an age-dependent decay in adult neurogenesis. Using unbiased stereological estimates of cell numbers, we detected an almost fivefold decrease in the number of mitotically active cells in the OT between young and old age. This reduced mitotic activity is paralleled by a reduction in DCX labeling. Finally, we detected a dramatic up-regulation of GFAP in the radial glia of the aged brain. This up-regulation is not paralleled by a similar up-regulation of S100B and Musashi-1, two other markers of the radial glia. In summary, the brain of N. furzeri replicates two typical hallmarks of mammalian aging: gliosis and reduced adult neurogenesis.
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