期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 594, 期 21, 页码 6395-6405出版社
WILEY
DOI: 10.1113/JP272907
关键词
Duchenne muscular dystrophy; MEMRI; sarcolemmal calcium influx
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01 AR061370]
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R21 NS085208]
- National Heart, Lung, and Blood Institute of the National Institutes of Health [T32 HL007676]
- Gillson Longenbaugh Foundation
- Welch Foundation [C-0627]
Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative disease resulting from a mutation in the gene that encodes dystrophin, leading to decreased muscle mechanical stability and force production. Increased Nox2 reactive oxygen species (ROS) production and sarcolemmal Ca2+ influx are early indicators of disease pathology, and eliminating Nox2 ROS production reduces aberrant Ca2+ influx in young mdx mice, a model of DMD. Various imaging modalities have been used to study dystrophic muscle in vivo; however, they are based upon alterations in muscle morphology or inflammation. Manganese has been used for indirect monitoring of calcium influx across the sarcolemma and may allow detection of molecular alterations in disease progression in vivo using manganese-enhanced magnetic resonance imaging (MEMRI). Therefore, we hypothesized that eliminating Nox2 ROS production would decrease calcium influx in adult mdx mice and that MEMRI would be able to monitor and differentiate disease status in dystrophic muscle. Both in vitro and in vivo data demonstrate that eliminating Nox2 ROS protected against aberrant Ca2+ influx and improved muscle function in dystrophic muscle. MEMRI was able to differentiate between different pathological states in vivo, with no long-term effects on animal health or muscle function. We conclude that MEMRI is a viable, non-invasive technique to differentiate disease status and might provide a means to monitor and evaluate the effectiveness of potential therapies in dystrophic muscle.
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