Wu Meina, He Yexin, Zhang Jun, Yang Junting, Qi Jinshun
Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China.
Department of Radiology, Shanxi Provincial People's Hospital, Taiyuan 030012, China.
Neurosci Lett. 2017 May 1;648:47-52. doi: 10.1016/j.neulet.2017.03.043. Epub 2017 Mar 27.
Apolipoprotein E4 (APOE4) allele located on chromosome 19 is a major genetic risk factor for developing Alzheimer's disease (AD). However, the direct effects of ApoE4 on the cognitive function and long-term synaptic plasticity have not fully investigated. At the same time, although amyloid beta protein (Aβ)-ApoE complexes are principal components of AD-associated brain damage, there is still lack of in vivo study on the effects of co-existed Aβ1-40 and ApoE4. In the present study, we examined the effects of ApoE4 on the spatial memory and hippocampal long term potentiation (LTP) by using Morris water maze test and in vivo field potential recording, compared the neurotoxicity of Aβ1-40 and ApoE4, and investigated the effects of co-application of Aβ1-40 and ApoE4 on cognitive behavior and synaptic plasticity. The results showed that intracerebrovenrticular (i.c.v.) injection of Aβ1-40 or ApoE4 significantly and similarly impaired spatial learning and memory, and depressed the high-frequency stimulus (HFS) induced LTP. Importantly, compared to the effects of Aβ1-40 or ApoE4 alone, co-injection of Aβ1-40 and ApoE4 produced much heavier damages in cognitive behaviors and long term synaptic plasticity. These results demonstrated that ApoE4 not only exerted direct neurotoxicity but also enhanced the neurotoxicity of Aβ1-40 on spatial cognitive function and hippocampal LTP, which maybe partly elucidates the mechanism by which APOE4 allele exerted negative effects as a major genetic risk factor for developing AD.
位于19号染色体上的载脂蛋白E4（APOE4）等位基因是患阿尔茨海默病（AD）的主要遗传风险因素。然而，ApoE4对认知功能和长期突触可塑性的直接影响尚未得到充分研究。同时，尽管β淀粉样蛋白（Aβ）-ApoE复合物是AD相关脑损伤的主要成分，但仍缺乏关于Aβ1-40和ApoE4共存影响的体内研究。在本研究中，我们通过Morris水迷宫试验和体内场电位记录来检测ApoE4对空间记忆和海马长时程增强（LTP）的影响，比较Aβ1-40和ApoE4的神经毒性，并研究Aβ1-40和ApoE4共同应用对认知行为和突触可塑性的影响。结果表明，脑室内（i.c.v.）注射Aβ1-40或ApoE4均显著且类似地损害空间学习和记忆，并抑制高频刺激（HFS）诱导的LTP。重要的是，与单独注射Aβ1-40或ApoE4的效果相比，共同注射Aβ1-40和ApoE4对认知行为和长期突触可塑性产生的损害要严重得多。这些结果表明，ApoE4不仅具有直接神经毒性，还增强了Aβ1-40对空间认知功能和海马LTP的神经毒性，这可能部分阐明了APOE4等位基因作为患AD主要遗传风险因素发挥负面影响的机制。
