Effects of muscle damage on 31phosphorus magnetic resonance spectroscopy indices of energetic status and sarcolemma integrity in young mdx mice |
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| Authors: | Christopher Lopez Abhinandan Batra Zahra Moslemi Andrew Rennick Kimberly Guice Huadong Zeng Glenn A. Walter Sean C. Forbes |
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| Affiliation: | 1. Department of Physical Therapy, University of Florida, Gainesville, Florida, USA;2. Advanced Magnetic Resonance Imaging and Spectroscopy Facility, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA;3. Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA |
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| Abstract: | 31Phosphorus magnetic resonance spectroscopy (31P-MRS) has been shown to detect altered energetic status (e.g. the ratio of inorganic phosphate to phosphocreatine: Pi/PCr), intracellular acid–base status, and free intracellular magnesium ([Mg2+]) in dystrophic muscle compared with unaffected muscle; however, the causes of these differences are not well understood. The purposes of this study were to examine 31P-MRS indices of energetic status and sarcolemma integrity in young mdx mice compared with wild-type and to evaluate the effects of downhill running to induce muscle damage on 31P-MRS indices in dystrophic muscle. In vivo 31P-MRS spectra were acquired from the posterior hindlimb muscles in young (4–10 weeks of age) mdx (C57BL/10ScSn-DMDmdx) and wild-type (C57BL/10ScSnJ) mice using an 11.1-T MR system. The flux of phosphate from PCr to ATP was estimated by 31P-MRS saturation transfer experiments. Relative concentrations of high-energy phosphates were measured, and intracellular pH and [Mg2+] were calculated. 1H2O-T2 was measured using single-voxel 1H-MRS from the gastrocnemius and soleus using a 4.7-T MR system. Downhill treadmill running was performed in a subset of mice. Young mdx mice were characterized by elevated 1H2O-T2 (p < 0.01), Pi/PCr (p = 0.02), PCr to ATP flux (p = 0.04) and histological inflammatory markers (p < 0.05) and reduced (p < 0.01) [Mg2+] compared with wild-type. Furthermore, 24 h after downhill running, an increase (p = 0.02) in Pi/PCr was observed in mdx and wild-type mice compared with baseline, and a decrease (p < 0.001) in [Mg2+] and a lower (p = 0.048) intracellular [H+] in damaged muscle regions of mdx mice were observed, consistent with impaired sarcolemma integrity. Overall, our findings demonstrate that 31P-MRS markers of energetic status and sarcolemma integrity are altered in young mdx compared with wild-type mice, and these indices are exacerbated following downhill running. |
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| Keywords: | downhill running energetics inflammation mdx muscle damage muscular dystrophy |
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