Impaired long-term memory retention: Common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice
Impaired long-term memory retention: Common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice
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DOI：
10.1016/j.bbr.2013.05.034
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发表时间：
2013-09-01
影响因子：
2.7
通讯作者：
Lipp, Hans-Peter
中科院分区：
文献类型：
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作者：
Ben Abdallah, Nada M. -B.;Filipkowski, Robert K.;Lipp, Hans-Peter
在成年啮齿类动物中，使用不同方法减少海马神经发生的实验通常会损害海马依赖性过程的表现。尽管如此，成人神经发生的功能相关性远未被解开，迄今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，这种差异可能是用于改变神经发生的方法特异性的程度的结果，而不是成人神经发生改变的程度。为了解决这个问题，我们集中在颅照射，最广泛使用的技术，以损害海马神经发生，从而诱导海马依赖性行为缺陷。为了研究该技术的特异性，我们因此将4-5个月大的雌性细胞周期蛋白D2敲除小鼠（缺乏嗅觉和海马神经发生的生理水平的模型）暴露于10戈伊的X射线剂量，据报道其特异性地影响瞬时扩增的前体。在1.5个月的恢复期后，进行行为测试并探测自发活动、习惯化、焦虑以及空间学习和记忆。在Morris水迷宫中的空间学习在所有实验组中是完整的。虽然空间记忆保留评估后24小时收购也是完整的，在所有小鼠，辐照野生型和细胞周期蛋白D2基因敲除小鼠显示记忆缺陷后一周收购。此外，我们观察到焦虑和运动活动依赖于用于改变神经发生的技术的测试的显着差异。然而，无论基因型如何，受辐射的小鼠都是过度活跃的，而细胞周期蛋白D2敲除小鼠在大多数测试中都是活动减退的，并显示出改变的习惯。本研究强调，不同的方法，旨在减少成年海马神经发生可能会导致不同的行为障碍有关的运动和焦虑。与此相反，空间长期记忆保持一致的改变后，这两种方法表明海马神经发生在这个认知过程中的一个合理的含义。(C)2013爱思唯尔有限公司版权所有。
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 24 h 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. (C) 2013 Elsevier B.V. All rights reserved.