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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 6792694, 15 pages
https://doi.org/10.1155/2017/6792694
Research Article

Antioxidant Treatment Reduces Formation of Structural Cores and Improves Muscle Function in RYR1Y522S/WT Mice

1Center for Research on Aging and Translational Medicine (CeSI-MeT), University G. d'Annunzio of Chieti, 66100 Chieti, Italy
2Department of Neuroscience, Imaging, and Clinical Sciences (DNICS), University G. d'Annunzio of Chieti, 66100 Chieti, Italy
3Department of General Pathology, University Estadual de Londrina, 86057-970 Londrina, PR, Brazil
4Department of Medicine and Aging Science (DMSI), University G. d'Annunzio of Chieti, 66100 Chieti, Italy

Correspondence should be addressed to Simona Boncompagni; ti.hcinu@ingapmocnob.anomis

Received 6 April 2017; Accepted 13 June 2017; Published 10 September 2017

Academic Editor: Marko D. Prokić

Copyright © 2017 Antonio Michelucci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Central core disease (CCD) is a congenital myopathy linked to mutations in the ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca2+ release channel of skeletal muscle. CCD is characterized by formation of amorphous cores within muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1Y522S/WT knock-in mice, carrying a human mutation in RYR1 linked to malignant hyperthermia (MH) with cores, oxidative stress is elevated and fibers present severe mitochondrial damage and cores. We treated RYR1Y522S/WT mice with N-acetylcysteine (NAC), an antioxidant provided ad libitum in drinking water for either 2 or 6 months. Our results show that 2 months of NAC treatment starting at 2 months of age, when mitochondrial and fiber damage was still minimal, (i) reduce formation of unstructured and contracture cores, (ii) improve muscle function, and (iii) decrease mitochondrial damage. The beneficial effect of NAC treatment is also evident following 6 months of treatment starting at 4 months of age, when structural damage was at an advanced stage. NAC exerts its protective effect likely by lowering oxidative stress, as supported by the reduction of 3-NT and SOD2 levels. This work suggests that NAC administration is beneficial to prevent mitochondrial damage and formation of cores and improve muscle function in RYR1Y522S/WT mice.