Eccentric Resistance Training Ameliorates Muscle Weakness in a Mouse Model of Idiopathic Inflammatory Myopathies

Abstract

Objective. High-force eccentric contractions (ECCs) have traditionally been excluded from rehabilitation programs that include patients with idiopathic inflammatory myopathies (IIMs) due to unverified fear of causing muscle damage and inflammation. In an IIM animal model that used mice with experimental autoimmune myositis (EAM), we undertook this study to investigate whether ECC training can safely and effectively be used to counteract muscle weakness in IIM.Methods. EAM was induced in BALB/c mice by immunization with 3 injections of myosin emulsified in Freund's complete adjuvant. Controls (n = 12) and mice with EAM (n = 12) were exposed to either an acute bout of 100 ECCs or 4 weeks of ECC training (20 ECCs every other day). To induce ECCs, plantar flexor muscles were electrically stimulated while the ankle was forcibly dorsiflexed.Results. Less cell damage, as assessed by Evans blue dye uptake, was observed in the muscles of mice with EAM, compared to controls, after an acute bout of 100 ECCs (P < 0.05). Maximum Ca 2+ -activated force was decreased in skinned gastrocnemius muscle fibers from mice with EAM, and this was accompanied by increased expression of endoplasmic reticulum (ER) stress proteins, including Gsp78 and Gsp94 (P < 0.05). ECC training prevented the decrease in force and the increase in ER stress proteins and also enhanced the expression and myofibrillar binding of small heat-shock proteins (HSPs) (P < 0.05), which can stabilize myofibrillar structure and function. Conclusion.ECC training protected against the reduction in myofibrillar force-generating capacity in an IIM mouse model, and this occurred via inhibition of ER stress responses and small HSP-mediated myofibrillar stabilization.

Improved skeletal muscle fatigue resistance in experimental autoimmune myositis mice following high-intensity interval training

“…Indeed, our data show that HIIT inhibited the increased amount of ER stress proteins Grp78, Grp94, and PERK in the skeletal muscle of EAM mice. This is in line with a previous study from our lab where EAM-induced upregulation of ER stress proteins, including Grp78 and Grp94, was attenuated by 4 weeks of high-intensity eccentric contraction training in EAM mice [ 31 ]. Taken together, our findings promote exercise as an important non-pharmacological approach for relieving ER stress and improving mitochondrial function.…”

“…EAM is induced by immunization with three injections of myosin emulsified in complete Freund’s adjuvant. Muscle function is impaired at the end of the immunization period where muscular inflammation is already established [ 31 , 32 ]. Intriguingly, we recently have reported that resistance training starting 1 day after the last immunization inhibits ER stress and restores muscle strength in mice with EAM [ 31 ].…”

“…Muscle function is impaired at the end of the immunization period where muscular inflammation is already established [ 31 , 32 ]. Intriguingly, we recently have reported that resistance training starting 1 day after the last immunization inhibits ER stress and restores muscle strength in mice with EAM [ 31 ]. In the present study, we tested the following hypotheses: (1) fatigue resistance is decreased in the muscle of mice with EAM due to the decreased mitochondrial oxidative capacity induced by ER stress and (2) HIIT combats these deleterious effects of EAM.…”

Preservation of shortening velocity and power output in single muscle fibres from patients with idiopathic inflammatory myopathies

“…1). This finding suggests that weakness in IIMs may, at least in part, be caused by dysfunction of the contractile apparatus, and has also been illustrated in mouse models (Coley et al 2012;Himori et al 2021).…”

Alpha B-Crystallin in Muscle Disease Prevention: The Role of Physical Activity

“…A similar effect has been described in mice with experimental autoimmune myositis, utilized as an IIM animal model. In this protocol, eccentric contractions (20 ECCs every other day for 4 weeks) in electrically-stimulated plantar flexor muscles prevented the decrease in force and the increase in endoplasmic reticulum (ER) stress proteins seen in untrained animals and also enhanced the expression and myofibrillar binding of HSPB1 and HSPPB5 [ 174 ].…”