The role of N-methyl-D-aspartate receptor in Alzheimer's disease

Abstract

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.