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Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function
Denervation contributes to loss of force-generating capacity in aged skeletal muscles, but problems with quantification of denervated fibers mean the precise impact of denervation on muscle function remains unclear. This study therefore looked to develop a reliable assay for identifying denervated m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147802/ https://www.ncbi.nlm.nih.gov/pubmed/36790689 http://dx.doi.org/10.1007/s10522-023-10021-6 |
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author | Lal, Navneet N. Cornwall, Jon Sheard, Philip W. |
author_facet | Lal, Navneet N. Cornwall, Jon Sheard, Philip W. |
author_sort | Lal, Navneet N. |
collection | PubMed |
description | Denervation contributes to loss of force-generating capacity in aged skeletal muscles, but problems with quantification of denervated fibers mean the precise impact of denervation on muscle function remains unclear. This study therefore looked to develop a reliable assay for identifying denervated muscle fibers, and used this to explore the impact of denervation on age-related force-generation in mouse skeletal muscle. Thirteen young (6-month-old) and 10 old (24-months-old) C57Bl/6 J female mice were utilized. Anaesthetized mice were infused with the fluorescent deoxyglucose analog 2[N-(7-nitrobenz-2-oxa-1,2-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG) and the tibial nerve was repeatedly stimulated to label active skeletal muscle fibers by activity-dependent uptake of 2-NBDG. Data on muscle force generation were acquired as part of the stimulation routine. Labeled muscles were removed, snap frozen, sectioned, and slide mounted. Sections were imaged to show accumulation of 2-NBDG in activated fibers and lack of 2-NBDG accumulation in quiescent (denervated) fibers, then processed using immunohistochemistry to allow collection of data on fiber number and morphology. Soleus muscles from older mice had nine times as many denervated fibers as those from young mice (average n = 36 vs 4, old vs young). Older muscles developed significantly more passive force and less specific force, but denervation only partly accounted for age-related deficits in specific force. Further investigations are required to definitively identify contributors to the decrease in force generation that remain unaccounted for. |
format | Online Article Text |
id | pubmed-10147802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-101478022023-04-30 Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function Lal, Navneet N. Cornwall, Jon Sheard, Philip W. Biogerontology Research Article Denervation contributes to loss of force-generating capacity in aged skeletal muscles, but problems with quantification of denervated fibers mean the precise impact of denervation on muscle function remains unclear. This study therefore looked to develop a reliable assay for identifying denervated muscle fibers, and used this to explore the impact of denervation on age-related force-generation in mouse skeletal muscle. Thirteen young (6-month-old) and 10 old (24-months-old) C57Bl/6 J female mice were utilized. Anaesthetized mice were infused with the fluorescent deoxyglucose analog 2[N-(7-nitrobenz-2-oxa-1,2-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG) and the tibial nerve was repeatedly stimulated to label active skeletal muscle fibers by activity-dependent uptake of 2-NBDG. Data on muscle force generation were acquired as part of the stimulation routine. Labeled muscles were removed, snap frozen, sectioned, and slide mounted. Sections were imaged to show accumulation of 2-NBDG in activated fibers and lack of 2-NBDG accumulation in quiescent (denervated) fibers, then processed using immunohistochemistry to allow collection of data on fiber number and morphology. Soleus muscles from older mice had nine times as many denervated fibers as those from young mice (average n = 36 vs 4, old vs young). Older muscles developed significantly more passive force and less specific force, but denervation only partly accounted for age-related deficits in specific force. Further investigations are required to definitively identify contributors to the decrease in force generation that remain unaccounted for. Springer Netherlands 2023-02-15 2023 /pmc/articles/PMC10147802/ /pubmed/36790689 http://dx.doi.org/10.1007/s10522-023-10021-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Lal, Navneet N. Cornwall, Jon Sheard, Philip W. Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title | Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title_full | Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title_fullStr | Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title_full_unstemmed | Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title_short | Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
title_sort | use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147802/ https://www.ncbi.nlm.nih.gov/pubmed/36790689 http://dx.doi.org/10.1007/s10522-023-10021-6 |
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