Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer's Disease

• Published in: Frontiers in aging neuroscience Vol. 13; p. 772980
• Main Authors: Xu, Le, Zhou, Yiying, Hu, Linbo, Jiang, Hongde, Dong, Yibei, Shen, Haowei, Lou, Zhongze, Yang, Siyu, Ji, Yunxin, Ruan, Liemin, Zhang, Xiaoqin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 30.11.2021; Frontiers Media S.A
• Subjects: Age; Alzheimer's disease; Animal models; Cognitive ability; cognitive behavior; dendritic morphology; Excitatory postsynaptic potentials; Glutamic acid receptors; Hippocampal plasticity; Hippocampus; Laboratory animals; Long-term potentiation; Memory; Morphology; N-Methyl-D-aspartic acid receptors; Neurodegenerative diseases; Neuroscience; NMDAR; Postsynaptic density proteins; Presenilin 1; Pyramidal cells; Short term memory; SNAP-25 protein; Spatial memory; Synaptic plasticity; dendritic morphology; NMDAR; synaptic plasticity; Alzheimer’s disease; cognitive behavior
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2021.772980

The N-methyl-D-aspartate receptor is a critical molecule for synaptic plasticity and cognitive function. Impaired synaptic plasticity is thought to contribute to the cognitive impairment associated with Alzheimer's disease (AD). However, the neuropathophysiological alterations of N-methyl-D-aspartate receptor (NMDAR) function and synaptic plasticity in hippocampal CA1 in transgenic rodent models of AD are still unclear. In the present study, APP/PS1 mice were utilized as a transgenic model of AD, which exhibited progressive cognitive impairment including defective working memory, recognition memory, and spatial memory starting at 6 months of age and more severe by 8 months of age. We found an impaired long-term potentiation (LTP) and reduced NMDAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs) in the hippocampal CA1 of APP/PS1 mice with 8 months of age. Golgi staining revealed that dendrites of pyramidal neurons had shorter length, fewer intersections, and lower spine density in APP/PS1 mice compared to control mice. Further, the reduced expression levels of NMDAR subunits, PSD95 and SNAP25 were observed in the hippocampus of APP/PS1 mice. These results suggest that NMDAR dysfunction, impaired synaptic plasticity, and disrupted neuronal morphology constitute an important part of the neuropathophysiological alterations associated with cognitive impairment in APP/PS1 mice.