Amyloid β-protein differentially affects NMDA receptor-and GABAA receptor-mediated currents in rat hippocampal CA1 neurons

作     者：Junfang Zhanga, Lei Houb, Xiuping Gao a, Fen Guoa, Wei Jingc, Jinshun Qia, Jiantian Qiaoa a Department of Neurobiology, Shanxi Medical University, Taiyuan 030001, China b Anesthesiology Department, Shanxi Tumor Hospital, Taiyuan 030013, China c Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China 

作者机构：Department of Neurobiology Shanxi Medical University Taiyuan 030001 China Anesthesiology Department Shanxi Tumor Hospital Taiyuan 030013 China Department of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200240 China 

出 版 物：《Progress in Natural Science:Materials International》 (自然科学进展·国际材料(英文))

年 卷 期：2009年第19卷第8期

页      面：963-972页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 

基　　金：supported by National Natural Science Foundation of China (Grant Nos. 30740095 and30840085) Education Ministry Special Foundation for High School’s Doctoral Program in China (20060114004) Natural Science Foundation of Shanxi Province of China(200601105) Natural Science Fund for Youths of Shanxi Province (2008021045-2) 

主　　题：Amyloid b-protein Glutamate-induced current GABA-induced current Whole-cell patch clamp Hippocampus 

摘      要：Although the aggregated amyloid b-protein (Ab) in senile plaques is one of the key neuropathological features of Alzheimer’s disease (AD), soluble forms of Ab also interfere with synaptic plasticity at the early stage of AD. The suppressive action of acute application of Ab on hippocampal long-term potentiation (LTP) has been reported widely, whereas the mechanism underlying the effects of Ab is still mostly unknown. The present study, using the whole-cell patch clamp technique, investigated the effects of Ab fragments (Ab25–35 and Ab31–35) on the LTP induction-related postsynaptic ligand-gated channel currents in isolated hippocampal CA1 neurons. The results showed a rapid but opposite action of both peptides on excitatory and inhibitory receptor currents. Glutamate application-induced currents weresuppressed by Ab25–35in a dose-dependent manner,andfurtherN-methyl-D-aspartate(NMDA)receptor-mediated currents were selectively inhibited. In contrast, pretreatment with Ab fragments potentiated c-aminobutyric acid (GABA)-induced whole-cell currents. As a control, Ab35–31, the reversed sequence of Ab31–35, showed no effect on the currents induced by glutamate, NMDA or GABA. These results may partly explain the impaired effects of Ab on hippocampal LTP, and suggest that the functional down-regulation of NMDA receptors and up-regulation of GABAA receptors may play an important role in remodeling the hippocampal synaptic plasticity in early AD.