A simulation model of neuroprogenitor proliferation dynamics predicts age-related loss of hippocampal neurogenesis but not astrogenesis.
A simulation model of neuroprogenitor proliferation dynamics predicts age-related loss of hippocampal neurogenesis but not astrogenesis.
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DOI：
10.1038/s41598-017-16466-3
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发表时间：
2017-11-28
影响因子：
4.6
通讯作者：
Sierra A
中科院分区：
文献类型：
--
作者：
Beccari S;Valero J;Maletic-Savatic M;Sierra A
成年的海马神经前体细胞既可以分化为神经元，也可以分化为星形胶质细胞。随着年龄的增长，神经前体细胞消失，神经发生也随之减少。然而，整个成年期神经元和星形胶质细胞的生成动力学还没有得到系统的研究。在这里，我们从纵向(从细胞寿命的2 h到30d)和横向(从1 m到12 m的年龄)分析了海马区的生态位，并建立了一个Marsaglia极随机模拟模型来预测新生细胞的动态。成年期新生神经元产量的急剧下降在很大程度上是由每个年龄段增殖的神经前体细胞的数量预测的。相反，在成年小鼠中，新生星形胶质细胞的衰退较慢，并与它们的产量增加有关。结果，随着年龄的增长，生态位从神经源转移到神经/星形。我们的数据提供了一个简单的“终点”模型，以了解成年后海马区的变化，并提示新生星形胶质细胞在老化的海马区回路中的功能尚未被探索。
Adult hippocampal neuroprogenitors give rise to both neurons and astrocytes. As neuroprogenitors are lost with increased age, neurogenesis concomitantly decreases. However, the dynamics of neuron and astrocyte generation throughout adulthood has not been systematically examined. Here, we analyzed the hippocampal niche both longitudinally (from 2 h to 30d of cell life) and transversally (from 1 m to 12 m of age) and generated a Marsaglia polar random simulation model to predict newborn cell dynamics. The sharp decrease in newborn neuron production throughout adulthood was largely predicted by the number of proliferating neuroprogenitors at each age. In contrast, newborn astrocyte decay was slower and associated with their increased yield in mature mice. As a result, the niche shifted from neurogenic to neuro/astrogenic with increased age. Our data provide a simple “end-point” model to understand the hippocampal niche changes across adulthood and suggest yet unexplored functions of newborn astrocytes for the aging hippocampal circuitry.
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