Department of Molecular Neurology, University Hospital Erlangen, Germany.
Behav Brain Res. 2013 Sep 1;252:275-86. doi: 10.1016/j.bbr.2013.05.034. Epub 2013 May 25.
In adult rodents, decreasing hippocampal neurogenesis experimentally using different approaches often impairs performance in hippocampus-dependent processes. Nonetheless, functional relevance of adult neurogenesis is far from being unraveled, and deficits so far described in animal models often lack reproducibility. One hypothesis is that such differences might be the consequence of the extent of the methodological specificity used to alter neurogenesis rather than the extent to which adult neurogenesis is altered. To address this, we focused on cranial irradiation, the most widely used technique to impair hippocampal neurogenesis and consequentially induce hippocampus-dependent behavioral deficits. To investigate the specificity of the technique, we thus exposed 4-5 months old female cyclin D2 knockout mice, a model lacking physiological levels of olfactory and hippocampal neurogenesis, to an X-ray dose of 10 Gy, reported to specifically affect transiently amplifying precursors. After a recovery period of 1.5 months, behavioral tests were performed and probed for locomotor activity, habituation, anxiety, and spatial learning and memory. Spatial learning in the Morris water maze was intact in all experimental groups. Although spatial memory retention assessed 24h following acquisition was also intact in all mice, irradiated wild type and cyclin D2 knockout mice displayed memory deficits one week after acquisition. In addition, we observed significant differences in tests addressing anxiety and locomotor activity dependent on the technique used to alter neurogenesis. Whereas irradiated mice were hyperactive regardless of their genotype, cyclin D2 knockout mice were hypoactive in most of the tests and displayed altered habituation. The present study emphasizes that different approaches aimed at decreasing adult hippocampal neurogenesis may result in distinct behavioral impairments related to locomotion and anxiety. In contrast, spatial long-term memory retention is consistently altered after both approaches suggesting a plausible implication of hippocampal neurogenesis in this cognitive process.
在成年啮齿动物中，通过不同方法实验性地减少海马神经发生通常会损害海马依赖过程的表现。尽管如此，成年神经发生的功能相关性还远未被揭示，而且到目前为止在动物模型中描述的缺陷往往缺乏可重复性。一种假设是，这种差异可能是由于改变神经发生的方法学特异性的程度，而不是改变成年神经发生的程度的结果。为了解决这个问题，我们专注于颅照射，这是最广泛用于损害海马神经发生并因此诱导海马依赖行为缺陷的技术。为了研究该技术的特异性，我们因此将缺乏生理水平的嗅觉和海马神经发生的 4-5 个月大的周期蛋白 D2 敲除小鼠暴露于 10Gy 的 X 射线剂量下，该剂量据报道专门影响短暂扩增前体。在 1.5 个月的恢复期后，进行行为测试，以探测运动活动、习惯化、焦虑和空间学习和记忆。所有实验组的 Morris 水迷宫空间学习都正常。尽管所有小鼠在获得后 24 小时评估的空间记忆保留也正常，但照射的野生型和周期蛋白 D2 敲除小鼠在获得后一周显示出记忆缺陷。此外，我们观察到依赖于改变神经发生的技术的焦虑和运动活动测试中的显著差异。尽管照射的小鼠无论基因型如何都表现出过度活跃，但周期蛋白 D2 敲除小鼠在大多数测试中表现出活动减少，并表现出习惯化改变。本研究强调，旨在减少成年海马神经发生的不同方法可能导致与运动和焦虑相关的不同行为损伤。相比之下，两种方法后空间长期记忆保留都发生改变，提示海马神经发生可能参与此认知过程。
