Impact of Heat Therapy on Skeletal Muscle Function in a Model of Duchenne Muscular Dystrophy

Bohyun Ro, Purdue University

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked disease that affects about 1 in 3,500 male births worldwide. Mutations in the DMD gene result in unstable or even the absence of dystrophin, a key protein that stabilizes the skeletal muscle cell membrane by mechanically linking the cytoskeleton and the extracellular matrix. Although there is no cure for this disease, glucocorticoids or physiotherapy are commonly used to delay the progression of the disease and the loss of ambulation. However, long-term use of glucocorticoids is associated with several severe side effects, including weight gain, bone demineralization, and not all patients have access to physiotherapy. Contrary to the aforementioned option for DMD, heat therapy (HT) has no side effects, is practical, inexpensive, and amenable to be used in a home setting without medical supervision. Our recent work revealed that daily exposure to HT reduces fat accrual, promotes an increase in relative muscle mass, and enhances force development. Based upon these previous reports, the aim of this study was to: (1) examine the impact of treatment temperature on the skeletal muscle adaptations in DBA/2J mice; and (2) determine the impact of repeated HT for 3 consecutive weeks (5 days a week, 30 min per session) on the body composition and skeletal muscle function in D2.mdx, a model of DMD. Aiming to define the optimal temperature for HT application using a heat chamber, DBA/2J mice were randomly allocated (n = 6) to a control group or one of three different HT regimens (37, 39, 41℃) and underwent the treatment daily for 3 weeks. The second series of experiments was designed to contrast and compare the physiological adaptations to HT at 39℃ or control treatment (n = 12) for 3 weeks in D2.mdx mice. We hypothesized that the beneficial effects of HT would be dependent on the treatment temperature, being most evident at mild temperatures (37 and 39℃). In addition, we hypothesized that repeated exposure to HT would promote an increase in muscle mass and strength, and increase mitochondrial content. In study 1, we observed that relative muscle mass of both EDL and soleus muscle was significantly higher in animals exposed to HT at 39℃ (EDL treatment main effect, p = 0.04, soleus treatment main effect, p = 0.02). Moreover, when EDL muscle force was normalized to the estimated cross-sectional area, the 39℃ group showed significantly greater maximal force (treatment main effect, p = 0.02) compared to the 41℃ group. There were no significant differences between groups in body composition, forelimb grip strength, soleus muscle function, and mitochondrial content in DBA/2J mice. The results of study 2 revealed that there were no significant differences between groups in relative muscle mass and contractile muscle function in D2.mdx mice. In conclusion, HT at 39℃ for 3 weeks does not improve muscle function or increase muscle mass in a mouse model of DMD. Future studies are needed to define whether different HT treatment protocols elicit beneficial adaptations in the DMD.

Degree

M.Sc.

Advisors

Roseguini, Purdue University.

Subject Area

Physical therapy|Design|Physiology|Disability studies|Morphology|Therapy

COinS