Meng Fan-Tao, Zhao Jun, Fang Hui, Liu Ya-Jing
a CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences , University of Science and Technology of China (USTC) , Hefei , Anhui , P.R. China and.
b Core Faculty Center for Life Sciences , USTC , Hefei , Anhui , P.R. China.
Stress. 2015;18(4):419-26. doi: 10.3109/10253890.2015.1040986. Epub 2015 May 4.
The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.
载脂蛋白E（ApoE）ε4等位基因（ApoE4）是阿尔茨海默病（AD）发病机制中的一个重要遗传风险因素。除遗传因素外，诸如应激等环境因素可能在AD发病机制中起关键作用。本研究旨在调查慢性应激条件下不同人类胶质纤维酸性蛋白（GFAP）-ApoE转基因成年雄性小鼠的焦虑样行为和认知变化。在旷场试验中，与相应的GFAP-ApoE3（ApoEε3等位基因）小鼠相比，未应激的GFAP-ApoE4转基因小鼠的焦虑样行为增加。与未应激的GFAP-ApoE3小鼠相比，应激的GFAP-ApoE3小鼠的焦虑样行为增加，但出乎意料的是，与未应激的GFAP-ApoE4小鼠相比，应激的GFAP-ApoE4小鼠的焦虑样行为减少。在新物体识别任务中，GFAP-ApoE4和GFAP-ApoE3小鼠在慢性应激后均表现出长期非空间记忆障碍。有趣的是，相对于未应激的GFAP-ApoE4转基因小鼠，仅在应激的GFAP-ApoE4雄性小鼠中观察到短期非空间记忆障碍（基于新物体识别任务）。此外，相对于未应激的GFAP-ApoE3转基因雄性小鼠，在应激的GFAP-ApoE3转基因雄性小鼠中观察到短期空间记忆障碍；然而，基于Y迷宫任务，与未应激的对照小鼠相比，GFAP-ApoE4转基因雄性小鼠的短期空间记忆表现并未降低。总之，我们的研究结果表明，慢性应激以ApoE异构体依赖性方式影响GFAP-ApoE转基因小鼠的焦虑样行为以及空间和非空间记忆。
