期刊
FRONTIERS IN AGING NEUROSCIENCE
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2021.772980
关键词
Alzheimer's disease; NMDAR; synaptic plasticity; cognitive behavior; dendritic morphology
资金
- Natural Science Foundation of Zhejiang Province [LQ20C090002]
- Major Social Development Special Foundation of Ningbo [2017C510010]
- Medical and Health Science and Technology Plan Project of Zhejiang Province [2019KY564]
In this study, APP/PS1 mice were used as a transgenic model of AD. The results showed impaired NMDAR function, synaptic plasticity, and disrupted neuronal morphology in the hippocampal CA1 of 8-month-old APP/PS1 mice, contributing to cognitive impairment.
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.
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