Zhang Junsi, Li Yanna, Xu Jing, Yang Zhou
College of Medicine, Tianjin Key Laboratory of Animal Models and Degenerative Neurological Diseases, Nankai University, Tianjin 300071, China.
College of Medicine, Tianjin Key Laboratory of Animal Models and Degenerative Neurological Diseases, Nankai University, Tianjin 300071, China.
J Neurol Sci. 2014 Apr 15;339(1-2):123-9. doi: 10.1016/j.jns.2014.01.041. Epub 2014 Feb 6.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive disorder and memory dysfunction. This kind of cognitive impairment is closely related to synaptic plasticity, in which N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, plays a critical role. Therefore the present study was designed to investigate whether the cognitive impairment of AD rat model has relation to the change of NMDAR. The adult male rats were randomly divided into three groups: control, AD and AD+APV (the competitive but not selective blocker of NMDAR) groups. The synaptic plasticity was measured by recording long-term potentiation (LTP) and depression (LTD) in the perforant path (PP) to dentate gyrus (DG) of hippocampus. The spatial memory and reversal learning were examined by Morris water maze (MWM) test. Results showed that the spatial learning performance of MWM was significantly impaired in AD group compared to that of control group. Rats of APV group showed a higher LTP and better performance in spatial memory, but worse performance in reversal learning test and lower LTD than those of AD group. In conclusion, the high concentration of APV influenced LTD and enhanced LTP in AD rats through changing the proportion of NMDAR, which suggested that the change of NMDAR may participate in the pathogenesis of AD at the synaptic level.
阿尔茨海默病（AD）是一种以认知障碍和记忆功能障碍为特征的神经退行性疾病。这种认知损害与突触可塑性密切相关，其中作为谷氨酸受体之一的N-甲基-D-天冬氨酸受体（NMDAR）起着关键作用。因此，本研究旨在探讨AD大鼠模型的认知损害是否与NMDAR的变化有关。成年雄性大鼠被随机分为三组：对照组、AD组和AD+APV（NMDAR的竞争性而非选择性阻断剂）组。通过记录海马齿状回（DG）穿通通路（PP）中的长时程增强（LTP）和长时程抑制（LTD）来测量突触可塑性。通过莫里斯水迷宫（MWM）试验检测空间记忆和逆向学习能力。结果显示，与对照组相比，AD组MWM的空间学习能力显著受损。APV组大鼠的LTP较高，空间记忆表现较好，但在逆向学习试验中的表现比AD组差，LTD也较低。总之，高浓度的APV通过改变NMDAR的比例影响AD大鼠的LTD并增强LTP，这表明NMDAR的变化可能在突触水平参与AD的发病机制。
