Garthe Alexander, Roeder Ingo, Kempermann Gerd
German Center for Neurodegenerative Diseases (DZNE) Dresden, Adult Neurogenesis, Dresden, Germany.
CRTD-DFG Research Center for Regenerative Therapies Dresden, Genomics of Regeneration, Technische Universität Dresden, Dresden, Germany.
Hippocampus. 2016 Feb;26(2):261-71. doi: 10.1002/hipo.22520. Epub 2015 Sep 15.
We here show that living in a stimulus-rich environment (ENR) improves water maze learning with respect to specific key indicators that in previous loss-of-function experiments have been shown to rely on adult hippocampal neurogenesis. Analyzing the strategies employed by mice to locate the hidden platform in the water maze revealed that ENR facilitated task acquisition by increasing the probability to use effective search strategies. ENR also enhanced the animals' behavioral flexibility, when the escape platform was moved to a new location. Treatment with temozolomide, which is known to reduce adult neurogenesis, abolished the effects of ENR on both acquisition and flexibility, while leaving other aspects of water maze learning untouched. These characteristic effects and interdependencies were not seen in parallel experiments with voluntary wheel running (RUN), a second pro-neurogenic behavioral stimulus. Since the histological assessment of adult neurogenesis is by necessity an end-point measure, the levels of neurogenesis over the course of the experiment can only be inferred and the present study focused on behavioral parameters as analytical endpoints. Although the correlation of physical activity with precursor cell proliferation and of learning and the survival of new neurons is well established, how the specific functional effects described here relate to dynamic changes in the stem cell niche remains to be addressed. Nevertheless, our findings support the hypothesis that adult neurogenesis is a critical mechanism underlying the beneficial effects of leading an active live, rich in experiences.
我们在此表明,生活在刺激丰富的环境(ENR)中,在特定关键指标方面可改善水迷宫学习,这些指标在先前的功能丧失实验中已被证明依赖于成年海马神经发生。分析小鼠在水迷宫中定位隐藏平台所采用的策略发现,ENR通过增加使用有效搜索策略的概率促进了任务获取。当逃生平台移至新位置时,ENR还增强了动物的行为灵活性。用已知可减少成年神经发生的替莫唑胺治疗,消除了ENR对获取和灵活性的影响,而水迷宫学习的其他方面则未受影响。在自愿轮转跑步(RUN)(另一种促神经发生的行为刺激)的平行实验中未观察到这些特征性影响和相互依赖性。由于成年神经发生的组织学评估必然是一种终点测量,实验过程中的神经发生水平只能推断得出,且本研究将行为参数作为分析终点。尽管身体活动与前体细胞增殖以及学习与新神经元存活之间的相关性已得到充分证实,但此处描述的特定功能效应与干细胞生态位的动态变化之间的关系仍有待探讨。然而,我们的研究结果支持这样的假设,即成年神经发生是积极生活、丰富经历产生有益影响的关键机制。