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Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease
BACKGROUND: The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weaknes...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794032/ https://www.ncbi.nlm.nih.gov/pubmed/24130765 http://dx.doi.org/10.1371/journal.pone.0076187 |
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author | Nalbandian, Angèle Nguyen, Christopher Katheria, Veeral Llewellyn, Katrina J. Badadani, Mallikarjun Caiozzo, Vincent Kimonis, Virginia E. |
author_facet | Nalbandian, Angèle Nguyen, Christopher Katheria, Veeral Llewellyn, Katrina J. Badadani, Mallikarjun Caiozzo, Vincent Kimonis, Virginia E. |
author_sort | Nalbandian, Angèle |
collection | PubMed |
description | BACKGROUND: The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases. METHODS/PRINCIPLE FINDINGS: The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+) mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+) mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype. CONCLUSIONS: Collectively, our data highlights that uphill exercise training in VCP(R155H/+) mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases. |
format | Online Article Text |
id | pubmed-3794032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37940322013-10-15 Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease Nalbandian, Angèle Nguyen, Christopher Katheria, Veeral Llewellyn, Katrina J. Badadani, Mallikarjun Caiozzo, Vincent Kimonis, Virginia E. PLoS One Research Article BACKGROUND: The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases. METHODS/PRINCIPLE FINDINGS: The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+) mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+) mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype. CONCLUSIONS: Collectively, our data highlights that uphill exercise training in VCP(R155H/+) mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases. Public Library of Science 2013-10-09 /pmc/articles/PMC3794032/ /pubmed/24130765 http://dx.doi.org/10.1371/journal.pone.0076187 Text en © 2013 Nalbandian et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nalbandian, Angèle Nguyen, Christopher Katheria, Veeral Llewellyn, Katrina J. Badadani, Mallikarjun Caiozzo, Vincent Kimonis, Virginia E. Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title | Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title_full | Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title_fullStr | Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title_full_unstemmed | Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title_short | Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease |
title_sort | exercise training reverses skeletal muscle atrophy in an experimental model of vcp disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794032/ https://www.ncbi.nlm.nih.gov/pubmed/24130765 http://dx.doi.org/10.1371/journal.pone.0076187 |
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