Sex influences diaphragm muscle response in exercised mdx mice

Abstract

Physical exercise promotes increased muscle damage in the mdx mice, the experimental model of Duchenne muscular dystrophy. Studies suggest that the estrogen level in females makes them less susceptible to muscle injuries. The aim of this study was to characterize the diaphragm (DIA) muscle response to physical exercise in male and female mdx mice. The animals were divided into four groups: female sedentary mdx; male sedentary mdx; female mdx submitted to exercise; and male mdx mice submitted to exercise. Blood samples were used to determine creatine kinase (CK). Regenerated muscle fibers were indicated by the presence of central nucleus and also inflammation areas were determined in DIA muscle sections. The alpha and beta estrogen receptors (ER) were determined by means of immunohistochemistry evaluation in the dystrophic DIA muscle. Male mdx animals submitted to exercise showed increased CK levels and inflammatory area. The quantification of regenerated fibers was higher in male animals, submitted or not to physical exercise. Greater alpha and beta ER expression was verified in the females submitted to exercise in the DIA muscle than in the other experimental groups. Therefore, estrogen may have contributed to the prevention of increased inflammatory process and DIA injury in females submitted to exercise.

Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

“…While estrogen deficiency did not affect skeletal muscle strength, fatigability, or recovery of strength after fatigue in both the diaphragm and anterior crural muscles of female mdx mice in this study, gender and age effects have been shown to impact skeletal muscle physiology of dystrophic mice [63,64]. For example, Hakim et al showed that maximal sP o of EDL muscle in 6 mo female mdx mice was greater than aged-matched male mdx mice [63].…”

Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin‐deficient mdx mice

“…Elevated CK levels are identified after physical activity, surgery and seizures 65 . It has previously been shown that physical demand leads to an exacerbation of CK serum concentration in mdx mice 66,67 …”

“…65 It has previously been shown that physical demand leads to an exacerbation of CK serum concentration in mdx mice. 66,67 The absence of dystrophin causes damage to the sarcolemma, inducing massive infiltration of immune cells, chronic inflammation, necrosis, and severe muscle degeneration 68,69 after muscle degradation. As well as depletion of regenerative capacity, fibrotic tissue is observed in the dystrophic muscle.…”