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首页> 外文期刊>The European Journal of Neuroscience >Physical exercise increases Notch activity, proliferation and cell cycle exit of type-3 progenitor cells in adult hippocampal neurogenesis.
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Physical exercise increases Notch activity, proliferation and cell cycle exit of type-3 progenitor cells in adult hippocampal neurogenesis.

机译：体育锻炼可提高成年海马神经发生中3型祖细胞的Notch活性，增殖和细胞周期退出。

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摘要

In adult hippocampal neurogenesis of mice, the proliferation of precursor cells can be stimulated by voluntary exercise (wheel-running). Physical activity has an additional effect on late progenitor cells (type-3) by promoting cell survival and further maturation. Notch1 is a key regulator of various steps in neuronal development, including the inhibition of cell cycle exit and neuronal differentiation of neural stem cells, as well as promoting the survival and dendritic branching of newborn neurons. We here report that physical activity increased the proportion and absolute number of doublecortin(+) (DCX) type-2b and type-3 progenitor cells that showed an activated Notch1 pathway. In contrast, the fraction of dividing cells with nuclear Notch intracellular domain expression indicating an activated Notch pathway was not affected by physical exercise. We used double labeling with two halogenated thymidine analogs, iododeoxyuridine and chlorodeoxyuridine, to distinguish between cell cycle exit and continued division at the progenitor cell level. After 7 days of physical exercise, the proliferative activity of precursor cells was increased, whereas the proportion of type-2b/3 cells re-entering S-phase was reduced. Consistent with this observation, the proportion of DCX(+) cells that expressed the marker of postmitotic immature granule cells (calretinin) was enhanced. Running promotes both the proliferation and cell cycle exit of DCX(+) type-3 precursors, possibly by preferentially stimulating a last neurogenic cell division. These pro-proliferative effects are independent of Notch1, whereas the running-induced survival and cell cycle exit of type-3 progenitor cells might by mediated by Notch1 activity.
机译：在成年小鼠海马神经发生中，自愿运动（滚轮运动）可以刺激前体细胞的增殖。体力活动通过促进细胞存活和进一步成熟，对晚期祖细胞（3型）具有附加作用。 Notch1是神经元发育各个步骤的关键调节剂，包括抑制细胞周期退出和神经干细胞的神经元分化，以及促进新生神经元的存活和树突分支。我们在这里报告的体育活动增加了比例和绝对数量的双皮质（+）（DCX）2b型和3型祖细胞显示激活的Notch1途径。相反，具有核刻缺蛋白胞内域表达的分裂细胞的分数表明激活的刻缺蛋白途径不受体育锻炼的影响。我们使用两个卤代胸苷类似物（碘代脱氧尿苷和氯代脱氧尿苷）进行双重标记，以区分细胞周期退出和祖细胞水平的继续分裂。经过7天的体育锻炼，前体细胞的增殖活性增加，而重新进入S期的2b / 3型细胞的比例减少。与该观察结果一致，表达有丝分裂后未成熟颗粒细胞（calretinin）标记的DCX（+）细胞比例增加。跑步可能通过优先刺激最后的神经源性细胞分裂来促进DCX（+）3型前体的增殖和细胞周期退出。这些促增殖作用独立于Notch1，而3型祖细胞的运行诱导存活和细胞周期退出可能是由Notch1活性介导的。

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