Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis

Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skel...

Descripción completa

Detalles Bibliográficos
Autores principales: Jensen, L., Jørgensen, L. H., Bech, R. D., Frandsen, U., Schrøder, H. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852332/
https://www.ncbi.nlm.nih.gov/pubmed/27195289
http://dx.doi.org/10.1155/2016/5930621
_version_ 1782429922797551616
author Jensen, L.
Jørgensen, L. H.
Bech, R. D.
Frandsen, U.
Schrøder, H. D.
author_facet Jensen, L.
Jørgensen, L. H.
Bech, R. D.
Frandsen, U.
Schrøder, H. D.
author_sort Jensen, L.
collection PubMed
description Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting.
format Online
Article
Text
id pubmed-4852332
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-48523322016-05-18 Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis Jensen, L. Jørgensen, L. H. Bech, R. D. Frandsen, U. Schrøder, H. D. Biomed Res Int Research Article Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting. Hindawi Publishing Corporation 2016 2016-04-18 /pmc/articles/PMC4852332/ /pubmed/27195289 http://dx.doi.org/10.1155/2016/5930621 Text en Copyright © 2016 L. Jensen et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jensen, L.
Jørgensen, L. H.
Bech, R. D.
Frandsen, U.
Schrøder, H. D.
Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title_full Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title_fullStr Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title_full_unstemmed Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title_short Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis
title_sort skeletal muscle remodelling as a function of disease progression in amyotrophic lateral sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852332/
https://www.ncbi.nlm.nih.gov/pubmed/27195289
http://dx.doi.org/10.1155/2016/5930621
work_keys_str_mv AT jensenl skeletalmuscleremodellingasafunctionofdiseaseprogressioninamyotrophiclateralsclerosis
AT jørgensenlh skeletalmuscleremodellingasafunctionofdiseaseprogressioninamyotrophiclateralsclerosis
AT bechrd skeletalmuscleremodellingasafunctionofdiseaseprogressioninamyotrophiclateralsclerosis
AT frandsenu skeletalmuscleremodellingasafunctionofdiseaseprogressioninamyotrophiclateralsclerosis
AT schrøderhd skeletalmuscleremodellingasafunctionofdiseaseprogressioninamyotrophiclateralsclerosis