Clark Peter J, Kohman Rachel A, Miller Daniel S, Bhattacharya Tushar K, Haferkamp Erik H, Rhodes Justin S
Department of Psychology, The Beckman Institute, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801, USA.
Behav Brain Res. 2010 Dec 1;213(2):246-52. doi: 10.1016/j.bbr.2010.05.007. Epub 2010 May 20.
Voluntary wheel running activates dentate gyrus granule neurons and increases adult hippocampal neurogenesis. Average daily running distance typically increases over a period of 3 weeks in rodents. Whether neurogenesis and cell activation are greater at the peak of running as compared to the initial escalation period is not known. Therefore, adult C57BL/6J male mice received 5 days of BrdU injections, at the same age, to label dividing cells during the onset of wheel access or after 21 days during peak levels of running or in sedentary conditions. Mice were sampled either 24h or 25 days after the last BrdU injection to measure cell proliferation and survival, respectively. Immunohistochemistry was performed on brain sections to identify the numbers of proliferating BrdU-labeled cells, and new neurons (BrdU/NeuN co-labeled) in the dentate gyrus. Ki67 was used as an additional mitotic marker. The induction of c-Fos was used to identify neurons activated from running. Mice ran approximately half as far during the first 5 days as compared to after 21 days. Running increased Ki67 cells at the onset but after 21 days levels were similar to sedentary. Numbers of BrdU cells were similar in all groups 24h after the final injection. However, after 25 days, running approximately doubled the survival of new neurons born either at the onset or peak of running. These changes co-varied with c-Fos expression. We conclude that sustained running maintains a stable rate of neurogenesis above sedentary via activity-dependent increases in differentiation and survival, not proliferation, of progenitor cells in the C57BL/6J model.
自愿性轮转跑步可激活齿状回颗粒神经元并增加成年海马神经发生。在啮齿动物中，平均每日跑步距离通常会在3周内增加。与初始递增期相比，在跑步高峰期神经发生和细胞激活是否更强尚不清楚。因此，成年C57BL/6J雄性小鼠在相同年龄接受5天的溴脱氧尿苷（BrdU）注射，以在开始使用跑步轮时或跑步高峰期21天后或久坐条件下标记分裂细胞。在最后一次BrdU注射后24小时或25天对小鼠进行采样，分别测量细胞增殖和存活情况。对脑切片进行免疫组织化学分析，以确定齿状回中增殖的BrdU标记细胞和新神经元（BrdU/NeuN共标记）的数量。Ki67用作额外的有丝分裂标记物。c-Fos的诱导用于识别因跑步而激活的神经元。与21天后相比，小鼠在最初5天的跑步距离约为一半。跑步在开始时增加了Ki67细胞，但21天后水平与久坐时相似。最后一次注射后24小时，所有组中的BrdU细胞数量相似。然而，25天后，跑步使在跑步开始或高峰期产生的新神经元的存活率增加了约一倍。这些变化与c-Fos表达共同变化。我们得出结论，在C57BL/6J模型中，持续跑步通过活动依赖性增加祖细胞的分化和存活而非增殖，维持了高于久坐状态的稳定神经发生速率。
