Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1181-9. doi: 10.1016/j.ijrobp.2015.12.364. Epub 2015 Dec 29.
To assess the influence of aging on hippocampal neuronal development after irradiation (IR).
Male mice, 2, 4, 6, 12, and 18 months of age, were given a single dose of 0 or 5 Gy of IR. A bromodeoxyuridine (BrdU) incorporation study was used to label newborn cells. Neural progenitors, newborn neurons, and microglia in dentate gyrus (DG) were identified by phenotypic markers, and their numbers were quantified by nonbiased stereology 9 weeks after IR.
BrdU-positive or newborn cells in DG decreased with aging and after IR. The number of neuroblasts and newborn neurons decreased with aging, and a further significant reduction was observed after IR. Total type 1 cells (the putative neural stem cells), and newborn type 1 cells decreased with aging, and further reduction in total type 1 cells was observed after IR. Aging-associated activation of microglia in hippocampus was enhanced after IR.
The aging-associated decline in hippocampal neurogenesis was further inhibited after IR. Ablation of neural progenitors and activation of microglia may contribute to the inhibition of neuronal development after IR across all ages.
评估辐射（IR）后衰老对海马神经元发育的影响。
雄性小鼠，2、4、6、12 和 18 个月大，给予 0 或 5 Gy 的单次 IR。使用溴脱氧尿苷（BrdU）掺入研究标记新生细胞。通过表型标志物鉴定齿状回（DG）中的神经前体细胞、新生神经元和小胶质细胞，并在 IR 后 9 周通过无偏立体学方法对其数量进行定量。
DG 中的 BrdU 阳性或新生细胞随年龄增长和 IR 而减少。神经母细胞和新生神经元的数量随年龄增长而减少，IR 后进一步显著减少。总 1 型细胞（潜在的神经干细胞）和新生 1 型细胞随年龄增长而减少，IR 后总 1 型细胞进一步减少。IR 后海马中小胶质细胞的衰老相关激活增强。
IR 后，与衰老相关的海马神经发生下降进一步受到抑制。神经前体细胞的消融和小胶质细胞的激活可能导致所有年龄段的神经元发育受到抑制。
