Overall Rupert W, Walker Tara L, Leiter Odette, Lenke Sina, Ruhwald Susann, Kempermann Gerd
CRTD - Center for Regenerative Therapies Dresden, Genomics of Regeneration, Technische Universität Dresden, Dresden, Germany.
CRTD - Center for Regenerative Therapies Dresden, Genomics of Regeneration, Technische Universität Dresden, Dresden, Germany ; German Center for Neurodegenerative Diseases (DZNE), Dresden, Dresden, Germany.
PLoS One. 2013 Dec 20;8(12):e83797. doi: 10.1371/journal.pone.0083797. eCollection 2013.
This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing) nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.
诸如小鼠转轮跑步等体育活动可增强普通小鼠品系C57BL/6成年海马体中的细胞增殖和神经发生，且神经发生的基线水平因品系而异，在DBA/2中显著更低。由于C57BL/6和DBA/2作为BXD重组近交系的亲本品系很重要，该重组近交系可用于检测调控诸如成年神经发生等表型的基因座，因此我们开展了本研究以探究调控神经发生的基因与环境的相互作用。在相同距离和时间跑步时，DBA/2J小鼠缺乏C57BL/6中已知的前体细胞增殖的急性增加。在DBA/2J中，增殖甚至与跑步距离呈负相关。这既不是由于应激反应（对跑步本身或单独饲养），也不是由于发情周期的差异。DBA/2动物表现出延迟且较弱的促神经发生反应，在转轮跑步超过一周后，增殖细胞数量才首次出现显著增加。两种品系对跑步的增殖反应都是短暂的，6周后效应就无法检测到。DBA/2J中新神经元的产生也有一个小的短暂增加，尽管这些额外的细胞没有存活下来。这些发现表明，C57BL/6和DBA/2之间的比较，以及由此延伸而来的源自这些品系的BXD遗传参考群体，应该为揭示影响成年海马体神经发生的活动依赖性调节的修饰基因复杂网络提供一个有力工具。更一般地说，我们的发现还描述了外部物理环境如何与内部遗传环境相互作用，以对相同的行为刺激产生不同的反应。
