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Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. He...

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Autores principales: Valdez, Gregorio, Tapia, Juan C., Lichtman, Jeff W., Fox, Michael A., Sanes, Joshua R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317643/
https://www.ncbi.nlm.nih.gov/pubmed/22485182
http://dx.doi.org/10.1371/journal.pone.0034640
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author Valdez, Gregorio
Tapia, Juan C.
Lichtman, Jeff W.
Fox, Michael A.
Sanes, Joshua R.
author_facet Valdez, Gregorio
Tapia, Juan C.
Lichtman, Jeff W.
Fox, Michael A.
Sanes, Joshua R.
author_sort Valdez, Gregorio
collection PubMed
description Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS.
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spelling pubmed-33176432012-04-06 Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles Valdez, Gregorio Tapia, Juan C. Lichtman, Jeff W. Fox, Michael A. Sanes, Joshua R. PLoS One Research Article Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS. Public Library of Science 2012-04-02 /pmc/articles/PMC3317643/ /pubmed/22485182 http://dx.doi.org/10.1371/journal.pone.0034640 Text en Valdez 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
Valdez, Gregorio
Tapia, Juan C.
Lichtman, Jeff W.
Fox, Michael A.
Sanes, Joshua R.
Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title_full Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title_fullStr Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title_full_unstemmed Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title_short Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles
title_sort shared resistance to aging and als in neuromuscular junctions of specific muscles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317643/
https://www.ncbi.nlm.nih.gov/pubmed/22485182
http://dx.doi.org/10.1371/journal.pone.0034640
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