Running Rescues Defective Adult Neurogenesis by Shortening the Length of the Cell Cycle of Neural Stem and Progenitor Cells
Running Rescues Defective Adult Neurogenesis by Shortening the Length of the Cell Cycle of Neural Stem and Progenitor Cells
复制标题
DOI：
10.1002/stem.1679
复制
发表时间：
2014-07-01
期刊：
影响因子：
5.2
通讯作者：
Tirone, Felice
中科院分区：
文献类型：
--
作者：
Farioli-Vecchioli, Stefano;Mattera, Andrea;Tirone, Felice
体育锻炼增加了成人神经发生中新神经元的生成。然而，只有少数研究调查了体育锻炼对神经发生受损范式的有益影响。在这里，我们证明，在缺乏抗增殖基因Btg1的小鼠中观察到，跑步完全逆转了海马和侧脑室室下区的成年神经发生缺陷。我们还首次评估了跑步如何影响野生型和btg1缺失小鼠的干细胞和前体亚群的细胞周期动力学，使用了一种新的方法来确定细胞周期长度。我们的数据显示，在野生型小鼠中，跑步只会导致神经d1阳性祖细胞的细胞周期缩短。相比之下，在btg1缺失的小鼠中，体育锻炼通过缩短神经干（胶质纤维酸性蛋白（+）和Sox2(+)）和祖细胞（NeuroD1(+)）的s期长度和整体细胞周期持续时间，完全重新激活有缺陷的海马神经发生。这些事件是充分和必要的，以重新激活在btg1缺失的早期产后小鼠中观察到的过度增殖，并扩大成体神经干细胞和祖细胞池。btg1缺失小鼠在跑步后细胞增殖的持续增加为新生神经元的增殖、分化和产生提供了长期的增加，从而挽救了先前在btg1缺失小鼠中发现的受损模式分离。这项研究表明，跑步对新生成神经元的特定亚群的细胞周期动力学有积极影响，并表明没有细胞周期抑制控制的神经干细胞的可塑性通过跑步被重新激活，这意味着神经发生的长期调节。
Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wildtype mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis.