Department of Neurobiology, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Neurodegener Dis. 2014;13(2-3):86-92. doi: 10.1159/000354777. Epub 2013 Sep 24.
We presently investigated the effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, on the cognitive performance of young targeted replacement apoE4 mice. We revealed that these mice were impaired in the object recognition and Morris water maze tests, both of which are associated with hippocampal learning and memory, relative to that of the apoE3 mice. These results are consistent with previous histological and biochemical findings that hippocampal neurons are specifically affected by apoE4. The suggestion that the behavioral impairments of the apoE4 mice are related to the hippocampal neuropathology of these mice is further supported by the fear conditioning test. This test revealed that the performance of the apoE4 mice in the contextual component, which is hippocampus related, was impaired, whereas their cued test response, which is amygdala driven, was not. The stress levels of the apoE4 and apoE3 mice, as unraveled by the light/dark anxiety test, were similar, suggesting that the observed cognitive impairments of the apoE4 mice are not related to differences in the basal anxiety levels of these mice. In conclusion, the present study shows that young apoE4 targeted replacement mice are impaired in numerous hippocampus-related learning and memory tasks.
我们目前研究了载脂蛋白 E4（apoE4）的影响，apoE4 是阿尔茨海默病最常见的遗传风险因素，对年轻的靶向替代 apoE4 小鼠的认知表现的影响。与 apoE3 小鼠相比，我们发现这些小鼠在物体识别和 Morris 水迷宫测试中表现受损，这两种测试都与海马体学习和记忆有关。这些结果与先前的组织学和生化研究结果一致，即海马体神经元特别受到 apoE4 的影响。apoE4 小鼠的行为损伤与这些小鼠的海马体神经病理学有关的观点进一步得到了恐惧条件反射测试的支持。该测试显示，apoE4 小鼠在与海马体相关的情境成分中的表现受损，而它们的提示测试反应（由杏仁核驱动）则没有。通过明暗焦虑测试揭示的 apoE4 和 apoE3 小鼠的应激水平相似，表明观察到的 apoE4 小鼠的认知损伤与这些小鼠的基础焦虑水平的差异无关。总之，本研究表明，年轻的 apoE4 靶向替代小鼠在许多与海马体相关的学习和记忆任务中受损。
