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Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease

Emerging evidence suggests that patients with Alzheimer’s disease (AD) may show accelerated sarcopenia phenotypes. To investigate whether pathological changes associated with neuronal death and cognitive dysfunction also occur in peripheral motor neurons and muscle as a function of age, we used the...

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Autores principales: Xu, Hongyang, Bhaskaran, Shylesh, Piekarz, Katarzyna M., Ranjit, Rojina, Bian, Jan, Kneis, Parker, Ellis, Aubrey, Bhandari, Suyesha, Rice, Heather C., Van Remmen, Holly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083113/
https://www.ncbi.nlm.nih.gov/pubmed/35547624
http://dx.doi.org/10.3389/fnagi.2022.876816
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author Xu, Hongyang
Bhaskaran, Shylesh
Piekarz, Katarzyna M.
Ranjit, Rojina
Bian, Jan
Kneis, Parker
Ellis, Aubrey
Bhandari, Suyesha
Rice, Heather C.
Van Remmen, Holly
author_facet Xu, Hongyang
Bhaskaran, Shylesh
Piekarz, Katarzyna M.
Ranjit, Rojina
Bian, Jan
Kneis, Parker
Ellis, Aubrey
Bhandari, Suyesha
Rice, Heather C.
Van Remmen, Holly
author_sort Xu, Hongyang
collection PubMed
description Emerging evidence suggests that patients with Alzheimer’s disease (AD) may show accelerated sarcopenia phenotypes. To investigate whether pathological changes associated with neuronal death and cognitive dysfunction also occur in peripheral motor neurons and muscle as a function of age, we used the triple transgenic mouse model of AD (3xTgAD mice) that carries transgenes for mutant forms of APP, Tau, and presenilin proteins that are associated with AD pathology. We measured changes in motor neurons and skeletal muscle function and metabolism in young (2 to 4 month) female control and 3xTgAD mice and in older (18–20 month) control and 3xTgAD female mice. In older 3xTgAD mice, we observed a number of sarcopenia-related phenotypes, including significantly fragmented and denervated neuromuscular junctions (NMJs) associated with a 17% reduction in sciatic nerve induced vs. direct muscle stimulation induced contractile force production, and a 30% decrease in gastrocnemius muscle mass. On the contrary, none of these outcomes were found in young 3xTgAD mice. We also measured an accumulation of amyloid-β (Aβ) in both skeletal muscle and neuronal tissue in old 3xTgAD mice that may potentially contribute to muscle atrophy and NMJ disruption in the older 3xTgAD mice. Furthermore, the TGF-β mediated atrophy signaling pathway is activated in old 3xTgAD mice and is a potential contributing factor in the muscle atrophy that occurs in this group. Perhaps surprisingly, mitochondrial oxygen consumption and reactive oxygen species (ROS) production are not elevated in skeletal muscle from old 3xTgAD mice. Together, these results provide new insights into the effect of AD pathological mechanisms on peripheral changes in skeletal muscle.
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spelling pubmed-90831132022-05-10 Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease Xu, Hongyang Bhaskaran, Shylesh Piekarz, Katarzyna M. Ranjit, Rojina Bian, Jan Kneis, Parker Ellis, Aubrey Bhandari, Suyesha Rice, Heather C. Van Remmen, Holly Front Aging Neurosci Neuroscience Emerging evidence suggests that patients with Alzheimer’s disease (AD) may show accelerated sarcopenia phenotypes. To investigate whether pathological changes associated with neuronal death and cognitive dysfunction also occur in peripheral motor neurons and muscle as a function of age, we used the triple transgenic mouse model of AD (3xTgAD mice) that carries transgenes for mutant forms of APP, Tau, and presenilin proteins that are associated with AD pathology. We measured changes in motor neurons and skeletal muscle function and metabolism in young (2 to 4 month) female control and 3xTgAD mice and in older (18–20 month) control and 3xTgAD female mice. In older 3xTgAD mice, we observed a number of sarcopenia-related phenotypes, including significantly fragmented and denervated neuromuscular junctions (NMJs) associated with a 17% reduction in sciatic nerve induced vs. direct muscle stimulation induced contractile force production, and a 30% decrease in gastrocnemius muscle mass. On the contrary, none of these outcomes were found in young 3xTgAD mice. We also measured an accumulation of amyloid-β (Aβ) in both skeletal muscle and neuronal tissue in old 3xTgAD mice that may potentially contribute to muscle atrophy and NMJ disruption in the older 3xTgAD mice. Furthermore, the TGF-β mediated atrophy signaling pathway is activated in old 3xTgAD mice and is a potential contributing factor in the muscle atrophy that occurs in this group. Perhaps surprisingly, mitochondrial oxygen consumption and reactive oxygen species (ROS) production are not elevated in skeletal muscle from old 3xTgAD mice. Together, these results provide new insights into the effect of AD pathological mechanisms on peripheral changes in skeletal muscle. Frontiers Media S.A. 2022-04-25 /pmc/articles/PMC9083113/ /pubmed/35547624 http://dx.doi.org/10.3389/fnagi.2022.876816 Text en Copyright © 2022 Xu, Bhaskaran, Piekarz, Ranjit, Bian, Kneis, Ellis, Bhandari, Rice and Van Remmen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Xu, Hongyang
Bhaskaran, Shylesh
Piekarz, Katarzyna M.
Ranjit, Rojina
Bian, Jan
Kneis, Parker
Ellis, Aubrey
Bhandari, Suyesha
Rice, Heather C.
Van Remmen, Holly
Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title_full Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title_fullStr Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title_full_unstemmed Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title_short Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
title_sort age related changes in muscle mass and force generation in the triple transgenic (3xtgad) mouse model of alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083113/
https://www.ncbi.nlm.nih.gov/pubmed/35547624
http://dx.doi.org/10.3389/fnagi.2022.876816
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