Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit

Abstract Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer’s disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechan...

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Autores principales:	Xinghua Liu, Kuan Zeng, Mengzhu Li, Qun Wang, Rong Liu, Bin Zhang, Jian-Zhi Wang, Xiji Shu, Xiaochuan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/61dfd11c4c5c4cc3a74545a38ef9dd36
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spelling	oai:doaj.org-article:61dfd11c4c5c4cc3a74545a38ef9dd362021-12-02T11:40:51ZExpression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit10.1038/s41598-017-04305-42045-2322https://doaj.org/article/61dfd11c4c5c4cc3a74545a38ef9dd362017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04305-4https://doaj.org/toc/2045-2322Abstract Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer’s disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit. We found that the exogenous mutant tau protein was restricted in MEC without spreading to other brain regions at one month after transduction. Interestingly, expression of the mutant tau in MEC induces endogenous tau hyperphosphorylation and accumulation in hippocampus and cortex, and inhibits neuronal activity with attenuated PP-DG synapse plasticity, leading to hippocampus-dependent memory deficit with intact olfactory function. These findings suggest a novel neuropathological mechanism of early AD, which is initiated by tau accumulation in MEC, and demonstrate a tau pathological model of early stage AD.Xinghua LiuKuan ZengMengzhu LiQun WangRong LiuBin ZhangJian-Zhi WangXiji ShuXiaochuan WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinghua Liu Kuan Zeng Mengzhu Li Qun Wang Rong Liu Bin Zhang Jian-Zhi Wang Xiji Shu Xiaochuan Wang Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
description	Abstract Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer’s disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit. We found that the exogenous mutant tau protein was restricted in MEC without spreading to other brain regions at one month after transduction. Interestingly, expression of the mutant tau in MEC induces endogenous tau hyperphosphorylation and accumulation in hippocampus and cortex, and inhibits neuronal activity with attenuated PP-DG synapse plasticity, leading to hippocampus-dependent memory deficit with intact olfactory function. These findings suggest a novel neuropathological mechanism of early AD, which is initiated by tau accumulation in MEC, and demonstrate a tau pathological model of early stage AD.
format	article
author	Xinghua Liu Kuan Zeng Mengzhu Li Qun Wang Rong Liu Bin Zhang Jian-Zhi Wang Xiji Shu Xiaochuan Wang
author_facet	Xinghua Liu Kuan Zeng Mengzhu Li Qun Wang Rong Liu Bin Zhang Jian-Zhi Wang Xiji Shu Xiaochuan Wang
author_sort	Xinghua Liu
title	Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
title_short	Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
title_full	Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
title_fullStr	Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
title_full_unstemmed	Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit
title_sort	expression of p301l-htau in mouse mec induces hippocampus-dependent memory deficit
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/61dfd11c4c5c4cc3a74545a38ef9dd36
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Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit

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