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Updated: Apr 24, 2026
Assessing Functional Performance in the Mdx Mouse Model
Published on: March 27, 2014
Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice
Francisco Altamirano1, Claudio F Perez2, Min Liu3
1Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
Abstract:
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by the absence of dystrophin in both skeletal and cardiac muscles. This leads to severe muscle degeneration, and dilated cardiomyopathy that produces patient death, which in most cases occurs before the end of the second decade. Several lines of evidence have shown that modulators of nitric oxide (NO) pathway can improve skeletal muscle and cardiac function in the mdx mouse, a mouse model for DMD. Whole body periodic acceleration (pGz) is produced by applying sinusoidal motion to supine humans and in standing conscious rodents in a headward-footward direction using a motion platform. It adds small pulses as a function of movement frequency to the circulation thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of NO. In this study, we examined the potential therapeutic properties of pGz for the treatment of skeletal muscle pathology observed in the mdx mouse. We found that pGz (480 cpm, 8 days, 1 hr per day) decreased intracellular Ca(2+) and Na(+) overload, diminished serum levels of creatine kinase (CK) and reduced intracellular accumulation of Evans Blue. Furthermore, pGz increased muscle force generation and expression of both utrophin and the carboxy-terminal PDZ ligand of nNOS (CAPON). Likewise, pGz (120 cpm, 12 h) applied in vitro to skeletal muscle myotubes reduced Ca(2+) and Na(+) overload, diminished abnormal sarcolemmal Ca(2+) entry and increased phosphorylation of endothelial NOS. Overall, this study provides new insights into the potential therapeutic efficacy of pGz as a non-invasive and non-pharmacological approach for the treatment of DMD patients through activation of the NO pathway.
Insights
Whole body periodic acceleration (pGz) therapy shows promise for Duchenne muscular dystrophy (DMD). This non-invasive treatment improved muscle function and reduced damage in mdx mice by activating the nitric oxide (NO) pathway.
Area of Science:
- Biomedical Engineering
- Muscle Physiology
- Cardiovascular Research
Background:
- Duchenne muscular dystrophy (DMD) is a severe genetic disorder causing progressive muscle degeneration and dilated cardiomyopathy due to dystrophin absence.
- Current treatments for DMD are limited, highlighting the need for novel therapeutic strategies.
- The nitric oxide (NO) pathway is implicated in improving skeletal and cardiac function in DMD models.
Purpose of the Study:
- To investigate the therapeutic potential of whole body periodic acceleration (pGz) for treating skeletal muscle pathology in mdx mice, a model for DMD.
- To explore the effects of pGz on intracellular ion levels, muscle damage markers, and muscle function.
- To assess the impact of pGz on the expression of key proteins like utrophin and CAPON, and endothelial nitric oxide synthase (eNOS) phosphorylation.
Main Methods:
- Mdx mice were subjected to whole body periodic acceleration (pGz) at 480 cycles per minute (cpm) for 1 hour daily over 8 days.
- In vitro studies applied pGz at 120 cpm for 12 hours to skeletal muscle myotubes.
- Measurements included intracellular calcium (Ca2+) and sodium (Na+) levels, serum creatine kinase (CK), Evans Blue accumulation, muscle force generation, utrophin and CAPON expression, and eNOS phosphorylation.
Main Results:
- pGz treatment significantly reduced intracellular Ca2+ and Na+ overload in mdx mouse skeletal muscles.
- Serum CK levels and Evans Blue accumulation, indicators of muscle damage, were diminished by pGz.
- pGz enhanced muscle force generation and increased the expression of utrophin and CAPON, while promoting eNOS phosphorylation in vitro.
Conclusions:
- Whole body periodic acceleration (pGz) demonstrates significant therapeutic efficacy in ameliorating skeletal muscle pathology in mdx mice.
- pGz acts as a non-invasive, non-pharmacological treatment by activating the nitric oxide (NO) pathway, reducing ion overload and muscle damage.
- These findings suggest pGz holds potential as a novel therapeutic approach for Duchenne muscular dystrophy patients.
