Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury

Gregory E. Bigford, Andrew J. Darr, Valerie C. Bracchi-Ricard, Han Gao, Mark S Nash, John R. Bethea

Research output: Contribution to journalArticle

Abstract

Spinal Cord Injury (SCI) results in severe sub-lesional muscle atrophy and fiber type transformation from slow oxidative to fast glycolytic, both contributing to functional deficits and maladaptive metabolic profiles. Therapeutic countermeasures have had limited success and muscle-related pathology remains a clinical priority. mTOR signaling is known to play a critical role in skeletal muscle growth and metabolism, and signal integration of anabolic and catabolic pathways. Recent studies show that the natural compound ursolic acid (UA) enhances mTOR signaling intermediates, independently inhibiting atrophy and inducing hypertrophy. Here, we examine the effects of UA treatment on sub-lesional muscle mTOR signaling, catabolic genes, and functional deficits following severe SCI in mice. We observe that UA treatment significantly attenuates SCI induced decreases in activated forms of mTOR, and signaling intermediates PI3K, AKT, and S6K, and the upregulation of catabolic genes including FOXO1, MAFbx, MURF-1, and PSMD11. In addition, UA treatment improves SCI induced deficits in body and sub-lesional muscle mass, as well as functional outcomes related to muscle function, motor coordination, and strength. These findings provide evidence that UA treatment may be a potential therapeutic strategy to improve muscle-specific pathological consequences of SCI.

Original languageEnglish (US)
Article numbere0203042
JournalPLoS One
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

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contusions
ursolic acid
Contusions
Pathology
Spinal Cord Injuries
spinal cord
Muscle
acid treatment
Muscles
muscles
therapeutics
muscular atrophy
Muscular Atrophy
Metabolome
phosphatidylinositol 3-kinase
Genes
atrophy
Phosphatidylinositol 3-Kinases
hypertrophy
muscle fibers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury. / Bigford, Gregory E.; Darr, Andrew J.; Bracchi-Ricard, Valerie C.; Gao, Han; Nash, Mark S; Bethea, John R.

In: PLoS One, Vol. 13, No. 8, e0203042, 01.08.2018.

Research output: Contribution to journalArticle

Bigford, Gregory E. ; Darr, Andrew J. ; Bracchi-Ricard, Valerie C. ; Gao, Han ; Nash, Mark S ; Bethea, John R. / Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury. In: PLoS One. 2018 ; Vol. 13, No. 8.
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