Differential Effects of Human P301L Tau Expression in Young versus Aged Mice

The greatest risk factor for developing Alzheimer’s disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utiliz...

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Autores principales:	Holly C. Hunsberger, Sharay E. Setti, Carolyn C. Rudy, Daniel S. Weitzner, Jeremiah C. Pfitzer, Kelli L. McDonald, Hao Hong, Subhrajit Bhattacharya, Vishnu Suppiramaniam, Miranda N. Reed
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease glutamate P301L tau aging Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/306c2dc9b1e94039b58557d8c900c0bd
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spelling	oai:doaj.org-article:306c2dc9b1e94039b58557d8c900c0bd2021-11-11T17:06:45ZDifferential Effects of Human P301L Tau Expression in Young versus Aged Mice10.3390/ijms2221116371422-00671661-6596https://doaj.org/article/306c2dc9b1e94039b58557d8c900c0bd2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11637https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The greatest risk factor for developing Alzheimer’s disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utilized mice harboring a regulatable mutant P301L human <i>tau</i> transgene (rTg(TauP301L)4510), in which P301L tau expression can be turned off or on by the addition or removal of doxycycline in the drinking water. This regulatable expression allowed for assessment of aging independent of prolonged mutant tau expression. Our results suggest that P301L expression in aged mice enhances memory deficits in the Morris water maze task. These behavioral changes may be due to enhanced late-stage tau pathology, as evidenced by immunoblotting and exacerbated hippocampal dysregulation of glutamate release and uptake measured by the microelectrode array technique. We additionally observed changes in proteins important for the regulation of glutamate and tau phosphorylation that may mediate these age-related changes. Thus, age and P301L tau interact to exacerbate tau-induced detrimental alterations in aged animals.Holly C. HunsbergerSharay E. SettiCarolyn C. RudyDaniel S. WeitznerJeremiah C. PfitzerKelli L. McDonaldHao HongSubhrajit BhattacharyaVishnu SuppiramaniamMiranda N. ReedMDPI AGarticleAlzheimer’s diseaseglutamateP301L tauagingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11637, p 11637 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease glutamate P301L tau aging Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer’s disease glutamate P301L tau aging Biology (General) QH301-705.5 Chemistry QD1-999 Holly C. Hunsberger Sharay E. Setti Carolyn C. Rudy Daniel S. Weitzner Jeremiah C. Pfitzer Kelli L. McDonald Hao Hong Subhrajit Bhattacharya Vishnu Suppiramaniam Miranda N. Reed Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
description	The greatest risk factor for developing Alzheimer’s disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utilized mice harboring a regulatable mutant P301L human <i>tau</i> transgene (rTg(TauP301L)4510), in which P301L tau expression can be turned off or on by the addition or removal of doxycycline in the drinking water. This regulatable expression allowed for assessment of aging independent of prolonged mutant tau expression. Our results suggest that P301L expression in aged mice enhances memory deficits in the Morris water maze task. These behavioral changes may be due to enhanced late-stage tau pathology, as evidenced by immunoblotting and exacerbated hippocampal dysregulation of glutamate release and uptake measured by the microelectrode array technique. We additionally observed changes in proteins important for the regulation of glutamate and tau phosphorylation that may mediate these age-related changes. Thus, age and P301L tau interact to exacerbate tau-induced detrimental alterations in aged animals.
format	article
author	Holly C. Hunsberger Sharay E. Setti Carolyn C. Rudy Daniel S. Weitzner Jeremiah C. Pfitzer Kelli L. McDonald Hao Hong Subhrajit Bhattacharya Vishnu Suppiramaniam Miranda N. Reed
author_facet	Holly C. Hunsberger Sharay E. Setti Carolyn C. Rudy Daniel S. Weitzner Jeremiah C. Pfitzer Kelli L. McDonald Hao Hong Subhrajit Bhattacharya Vishnu Suppiramaniam Miranda N. Reed
author_sort	Holly C. Hunsberger
title	Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
title_short	Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
title_full	Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
title_fullStr	Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
title_full_unstemmed	Differential Effects of Human P301L Tau Expression in Young versus Aged Mice
title_sort	differential effects of human p301l tau expression in young versus aged mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/306c2dc9b1e94039b58557d8c900c0bd
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Differential Effects of Human P301L Tau Expression in Young versus Aged Mice

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