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

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-aspartat...

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Autores principales:	Le Xu, Yiying Zhou, Linbo Hu, Hongde Jiang, Yibei Dong, Haowei Shen, Zhongze Lou, Siyu Yang, Yunxin Ji, Liemin Ruan, Xiaoqin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Alzheimer’s disease NMDAR synaptic plasticity cognitive behavior dendritic morphology Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/9c447a19b53345eb82f8cce314184e82
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spelling	oai:doaj.org-article:9c447a19b53345eb82f8cce314184e822021-12-01T18:21:30ZDeficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease1663-436510.3389/fnagi.2021.772980https://doaj.org/article/9c447a19b53345eb82f8cce314184e822021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.772980/fullhttps://doaj.org/toc/1663-4365The 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.Le XuLe XuYiying ZhouYiying ZhouLinbo HuHongde JiangYibei DongHaowei ShenHaowei ShenZhongze LouZhongze LouSiyu YangYunxin JiLiemin RuanXiaoqin ZhangXiaoqin ZhangFrontiers Media S.A.articleAlzheimer’s diseaseNMDARsynaptic plasticitycognitive behaviordendritic morphologyNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease NMDAR synaptic plasticity cognitive behavior dendritic morphology Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Alzheimer’s disease NMDAR synaptic plasticity cognitive behavior dendritic morphology Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Le Xu Le Xu Yiying Zhou Yiying Zhou Linbo Hu Hongde Jiang Yibei Dong Haowei Shen Haowei Shen Zhongze Lou Zhongze Lou Siyu Yang Yunxin Ji Liemin Ruan Xiaoqin Zhang Xiaoqin Zhang Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
description	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.
format	article
author	Le Xu Le Xu Yiying Zhou Yiying Zhou Linbo Hu Hongde Jiang Yibei Dong Haowei Shen Haowei Shen Zhongze Lou Zhongze Lou Siyu Yang Yunxin Ji Liemin Ruan Xiaoqin Zhang Xiaoqin Zhang
author_facet	Le Xu Le Xu Yiying Zhou Yiying Zhou Linbo Hu Hongde Jiang Yibei Dong Haowei Shen Haowei Shen Zhongze Lou Zhongze Lou Siyu Yang Yunxin Ji Liemin Ruan Xiaoqin Zhang Xiaoqin Zhang
author_sort	Le Xu
title	Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
title_short	Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
title_full	Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
title_fullStr	Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
title_full_unstemmed	Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
title_sort	deficits in n-methyl-d-aspartate receptor function and synaptic plasticity in hippocampal ca1 in app/ps1 mouse model of alzheimer’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9c447a19b53345eb82f8cce314184e82
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Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease

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