Effects of muscle damage on 31phosphorus magnetic resonance spectroscopy indices of energetic status and sarcolemma integrity in young mdx mice. (28th November 2021)

• Record Type: Journal Article
• Authors: Lopez, Christopher; Batra, Abhinandan; Moslemi, Zahra; Rennick, Andrew; Guice, Kimberly; Zeng, Huadong; Walter, Glenn A.; Forbes, Sean C.
• Is Part Of: NMR in biomedicine. Volume 35:Number 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-28
• Subjects: downhill running -- energetics -- inflammation -- mdx -- muscle damage -- muscular dystrophy; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.4659
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : 31 Phosphorus magnetic resonance spectroscopy ( 31 P‐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 ([Mg 2+ ]) 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 31 P‐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 31 P‐MRS indices in dystrophic muscle. In vivo 31 P‐MRS spectra were acquired from the posterior hindlimb muscles in young (4–10 weeks of age) mdx (C57BL/10ScSn‐DMD mdx ) and wild‐type (C57BL/10ScSnJ) mice using an 11.1‐T MR system. The flux of phosphate from PCr to ATP was estimated by 31 P‐MRS saturation transfer experiments. Relative concentrations of high‐energy phosphates were measured, and intracellular pH and [Mg 2+ ] were calculated. 1 H2 O‐T2 was measured using single‐voxel 1 H‐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 1 H2 O‐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) [Mg 2+ ] 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 [Mg 2+ ] 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 31 P‐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. Abstract : In this study, we observed that 31 P‐MRS markers of energetic status (ratio of inorganic phosphate to phosphocreatine) and sarcolemma integrity (intracellular free magnesium and acid–base status) were altered in skeletal muscle (hindlimbs) of young dystrophic mice ( mdx ) compared with wild‐type mice, and these indices were further exacerbated following downhill running. Our findings support that 31 P‐MRS may be valuable to monitor disease status and evaluate therapeutic interventions in dystrophic muscle.