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Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model

Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was ba...

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Autores principales: Bodea, Liviu‐Gabriel, Evans, Harrison Tudor, Van der Jeugd, Ann, Ittner, Lars M., Delerue, Fabien, Kril, Jillian, Halliday, Glenda, Hodges, John, Kiernan, Mathew C., Götz, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334525/
https://www.ncbi.nlm.nih.gov/pubmed/28160413
http://dx.doi.org/10.1111/acel.12565
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author Bodea, Liviu‐Gabriel
Evans, Harrison Tudor
Van der Jeugd, Ann
Ittner, Lars M.
Delerue, Fabien
Kril, Jillian
Halliday, Glenda
Hodges, John
Kiernan, Mathew C.
Götz, Jürgen
author_facet Bodea, Liviu‐Gabriel
Evans, Harrison Tudor
Van der Jeugd, Ann
Ittner, Lars M.
Delerue, Fabien
Kril, Jillian
Halliday, Glenda
Hodges, John
Kiernan, Mathew C.
Götz, Jürgen
author_sort Bodea, Liviu‐Gabriel
collection PubMed
description Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back‐crossed more than ten times onto a senescence‐accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus. Analysis of age‐matched SApT mice revealed that pathological tau phosphorylation was increased in these brain regions compared to those in the parental pR5 strain. Moreover, as revealed by immunohistochemistry, phosphorylation of critical tau phospho‐epitopes (P‐Ser202/P‐Ser205 and P‐Ser235) was significantly increased in the amygdala of SApT mice in an age‐dependent manner, suggesting an age‐associated effect of tau phosphorylation. Anxiety tests revealed that the older cohort of SApT mice (10 months vs. 8 months) exhibited a behavioural pattern similar to that observed for age‐matched tau transgenic pR5 mice and not the SAMP8 parental mice. Learning and memory, however, appeared to be governed by the accelerated aging background of the SAMP8 strain, as at both ages investigated, SAMP8 and SApT mice showed a decreased learning capacity compared to pR5 mice. We therefore conclude that accelerated aging exacerbates pathological tau phosphorylation, leading to changes in normal behaviour. These findings further suggest that SApT mice may be a useful novel model in which to study the role of a complex geriatric phenotype in tauopathy.
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spelling pubmed-53345252017-04-01 Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model Bodea, Liviu‐Gabriel Evans, Harrison Tudor Van der Jeugd, Ann Ittner, Lars M. Delerue, Fabien Kril, Jillian Halliday, Glenda Hodges, John Kiernan, Mathew C. Götz, Jürgen Aging Cell Original Articles Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back‐crossed more than ten times onto a senescence‐accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus. Analysis of age‐matched SApT mice revealed that pathological tau phosphorylation was increased in these brain regions compared to those in the parental pR5 strain. Moreover, as revealed by immunohistochemistry, phosphorylation of critical tau phospho‐epitopes (P‐Ser202/P‐Ser205 and P‐Ser235) was significantly increased in the amygdala of SApT mice in an age‐dependent manner, suggesting an age‐associated effect of tau phosphorylation. Anxiety tests revealed that the older cohort of SApT mice (10 months vs. 8 months) exhibited a behavioural pattern similar to that observed for age‐matched tau transgenic pR5 mice and not the SAMP8 parental mice. Learning and memory, however, appeared to be governed by the accelerated aging background of the SAMP8 strain, as at both ages investigated, SAMP8 and SApT mice showed a decreased learning capacity compared to pR5 mice. We therefore conclude that accelerated aging exacerbates pathological tau phosphorylation, leading to changes in normal behaviour. These findings further suggest that SApT mice may be a useful novel model in which to study the role of a complex geriatric phenotype in tauopathy. John Wiley and Sons Inc. 2017-02-04 2017-04 /pmc/articles/PMC5334525/ /pubmed/28160413 http://dx.doi.org/10.1111/acel.12565 Text en © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Bodea, Liviu‐Gabriel
Evans, Harrison Tudor
Van der Jeugd, Ann
Ittner, Lars M.
Delerue, Fabien
Kril, Jillian
Halliday, Glenda
Hodges, John
Kiernan, Mathew C.
Götz, Jürgen
Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title_full Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title_fullStr Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title_full_unstemmed Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title_short Accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
title_sort accelerated aging exacerbates a pre‐existing pathology in a tau transgenic mouse model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334525/
https://www.ncbi.nlm.nih.gov/pubmed/28160413
http://dx.doi.org/10.1111/acel.12565
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