Short-term and long-term survival of new neurons in the rat dentate gyrus

Short-term and long-term survival of new neurons in the rat dentate gyrus
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DOI:
10.1002/cne.10675
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发表时间:
2003-06-09
影响因子:
2.5
通讯作者:
Cameron, HA
Cameron, HA
中科院分区:
医学3区
文献类型:
--
作者:
Dayer, AG;Ford, AA;Cameron, HA

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在成年期,齿状回继续产生新的神经元。先前的研究表明,在2周内,有相当比例的胸腺嘧啶类似物溴脱氧尿嘧啶(bromodeoxyuridine, BrdU)标记的新颗粒细胞从成人齿状回丢失。这种损失持续多久,以及它在多大程度上代表细胞死亡,而不是标签的稀释,目前还不清楚。为了解决这些问题,我们给成年大鼠注射BrdU,并在几个生存时间点比较齿状回中BrdU的标记。BrdU和细胞周期标记物Ki-67的双重标记表明,BrdU在一些继续分裂的细胞中可检测到长达4天的时间,这表明BrdU标记的细胞数量在4天后的减少可能反映了细胞死亡,而不是BrdU稀释。标记后6至28天,颗粒细胞层中新细胞以稳定的速度死亡,在这22天期间,brdu标记的细胞损失了50%。在第一个月存活下来的新颗粒细胞至少又存活了5个月。相比之下,在出生后第6天齿状回发育高峰期标记BrdU的颗粒细胞在标记后1至6个月内死亡的比例为26%。这些发现表明,成年期出生的颗粒细胞整合到神经回路中并存活到成熟,这些颗粒细胞非常稳定,可能永久性地取代发育期间出生的颗粒细胞。2003年Wiley-Liss出版。
New neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki-67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU-Iabeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU-labeled cells over this 22-day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development. Published 2003 Wiley-Liss, Inc.