Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model

J. Spaas*, P. Van Noten, C. Keytsman, I. Nieste, L. Blancquaert, W. Derave, B.O. Eijnde

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE.
Original languageEnglish
Pages (from-to)1749-1761
Number of pages13
JournalAmino Acids
Issue number11
Early online date12 Oct 2021
Publication statusPublished - Nov 2021


  • Multiple sclerosis
  • Experimental autoimmune encephalomyelitis
  • Carnosine
  • Histidine-containing dipeptides
  • Skeletal muscle


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