A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice

Abstract Spinal cord injury (SCI) leads to rapid muscle atrophy due to paralysis/paresis and subsequent disuse. SS‐31 is a mitochondrial‐targeting peptide that has shown efficacy in protecting skeletal muscle mass and function in non‐SCI models of muscle wasting. We aimed to determine if SS‐31 could...

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Main Authors: Zachary A. Graham, Jennifer J. DeBerry, Christopher P. Cardozo, Marcas M. Bamman
Format: Article
Language:English
Published: Wiley 2021-02-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.14751
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author Zachary A. Graham
Jennifer J. DeBerry
Christopher P. Cardozo
Marcas M. Bamman
author_facet Zachary A. Graham
Jennifer J. DeBerry
Christopher P. Cardozo
Marcas M. Bamman
author_sort Zachary A. Graham
collection DOAJ
description Abstract Spinal cord injury (SCI) leads to rapid muscle atrophy due to paralysis/paresis and subsequent disuse. SS‐31 is a mitochondrial‐targeting peptide that has shown efficacy in protecting skeletal muscle mass and function in non‐SCI models of muscle wasting. We aimed to determine if SS‐31 could prevent muscle loss after SCI. Male C57BL/6 mice aged 9 weeks underwent sham surgery or 50 kdyne contusion SCI and were administered daily injections of vehicle or 5 mg/kg SS‐31 for 14 d. Both SCI groups had sustained losses in body mass compared to Sham animals and ~10% reductions in gastrocnemius, plantaris and tibialis anterior muscle mass after SCI with no clear effect of SS‐31. Measurements of protein synthesis in the soleus and plantaris were similar among all groups. mRNA expression of atrophy‐associated proinflammatory cytokines was also similar among all groups. There was elevation in MYH7 mRNA and a statistical reduction in MYH2 mRNA expression in the SCI+SS‐31 animals compared to Sham animals. There was an SCI‐induced reduction in mRNA expression of the E3 ligase FBXO32 (MAFbx), but no effect of SS‐31. In summary, a 50 kdyne contusion SCI was able to reduce body mass but was not associated with substantial muscle atrophy or alterations in gene expression profiles associated with muscle health and function 14 d post‐injury. SS‐31 was not associated with protection against SCI‐related changes in body or muscle mass, protein synthesis or gene expression in hindlimb muscles.
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spelling doaj.art-ee36c501dd804c9a9def57a62cfaad182022-12-21T22:39:49ZengWileyPhysiological Reports2051-817X2021-02-0194n/an/a10.14814/phy2.14751A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male miceZachary A. Graham0Jennifer J. DeBerry1Christopher P. Cardozo2Marcas M. Bamman3Research Service Birmingham VA Medical Center Birmingham AL USADepartment of Anesthesiology and Perioperative Medicine University of Alabama‐Birmingham Birmingham AL USANational Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center Bronx NY USAResearch Service Birmingham VA Medical Center Birmingham AL USAAbstract Spinal cord injury (SCI) leads to rapid muscle atrophy due to paralysis/paresis and subsequent disuse. SS‐31 is a mitochondrial‐targeting peptide that has shown efficacy in protecting skeletal muscle mass and function in non‐SCI models of muscle wasting. We aimed to determine if SS‐31 could prevent muscle loss after SCI. Male C57BL/6 mice aged 9 weeks underwent sham surgery or 50 kdyne contusion SCI and were administered daily injections of vehicle or 5 mg/kg SS‐31 for 14 d. Both SCI groups had sustained losses in body mass compared to Sham animals and ~10% reductions in gastrocnemius, plantaris and tibialis anterior muscle mass after SCI with no clear effect of SS‐31. Measurements of protein synthesis in the soleus and plantaris were similar among all groups. mRNA expression of atrophy‐associated proinflammatory cytokines was also similar among all groups. There was elevation in MYH7 mRNA and a statistical reduction in MYH2 mRNA expression in the SCI+SS‐31 animals compared to Sham animals. There was an SCI‐induced reduction in mRNA expression of the E3 ligase FBXO32 (MAFbx), but no effect of SS‐31. In summary, a 50 kdyne contusion SCI was able to reduce body mass but was not associated with substantial muscle atrophy or alterations in gene expression profiles associated with muscle health and function 14 d post‐injury. SS‐31 was not associated with protection against SCI‐related changes in body or muscle mass, protein synthesis or gene expression in hindlimb muscles.https://doi.org/10.14814/phy2.14751paralysisskeletal musclespinal cord injurySS‐31
spellingShingle Zachary A. Graham
Jennifer J. DeBerry
Christopher P. Cardozo
Marcas M. Bamman
A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
Physiological Reports
paralysis
skeletal muscle
spinal cord injury
SS‐31
title A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
title_full A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
title_fullStr A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
title_full_unstemmed A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
title_short A 50 kdyne contusion spinal cord injury with or without the drug SS‐31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
title_sort 50 kdyne contusion spinal cord injury with or without the drug ss 31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice
topic paralysis
skeletal muscle
spinal cord injury
SS‐31
url https://doi.org/10.14814/phy2.14751
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