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Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model

The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron l...

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Autores principales: Hüttenrauch, M, Brauß, A, Kurdakova, A, Borgers, H, Klinker, F, Liebetanz, D, Salinas-Riester, G, Wiltfang, J, Klafki, H W, Wirths, O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070068/
https://www.ncbi.nlm.nih.gov/pubmed/27138799
http://dx.doi.org/10.1038/tp.2016.65
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author Hüttenrauch, M
Brauß, A
Kurdakova, A
Borgers, H
Klinker, F
Liebetanz, D
Salinas-Riester, G
Wiltfang, J
Klafki, H W
Wirths, O
author_facet Hüttenrauch, M
Brauß, A
Kurdakova, A
Borgers, H
Klinker, F
Liebetanz, D
Salinas-Riester, G
Wiltfang, J
Klafki, H W
Wirths, O
author_sort Hüttenrauch, M
collection PubMed
description The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.
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spelling pubmed-50700682016-10-19 Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model Hüttenrauch, M Brauß, A Kurdakova, A Borgers, H Klinker, F Liebetanz, D Salinas-Riester, G Wiltfang, J Klafki, H W Wirths, O Transl Psychiatry Original Article The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia. Nature Publishing Group 2016-05 2016-05-03 /pmc/articles/PMC5070068/ /pubmed/27138799 http://dx.doi.org/10.1038/tp.2016.65 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Hüttenrauch, M
Brauß, A
Kurdakova, A
Borgers, H
Klinker, F
Liebetanz, D
Salinas-Riester, G
Wiltfang, J
Klafki, H W
Wirths, O
Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title_full Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title_fullStr Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title_full_unstemmed Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title_short Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
title_sort physical activity delays hippocampal neurodegeneration and rescues memory deficits in an alzheimer disease mouse model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070068/
https://www.ncbi.nlm.nih.gov/pubmed/27138799
http://dx.doi.org/10.1038/tp.2016.65
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