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Chemical sympathectomy ameliorates the dystrophic pathology of limb and diaphragm muscles in mdx mice
Author(s) -
Li Xilong,
Ye Jianfeng,
Thomas Gail D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb116-c
Subject(s) - duchenne muscular dystrophy , dystrophin , hindlimb , mdx mouse , muscular dystrophy , diaphragm (acoustics) , endocrinology , medicine , anatomy , dystrophy , gastrocnemius muscle , sympathectomy , skeletal muscle , pathology , physics , acoustics , loudspeaker
Mutations of the dystrophin gene cause Duchenne muscular dystrophy, but the pathogenetic mechanisms are poorly understood. We previously showed that vasoconstriction evoked by activation of sympathetic nerves or vascular α‐adrenoceptors is enhanced in dystrophin‐deficient muscles during exercise. We therefore hypothesized that sympathetically‐mediated muscle ischemia might contribute to the dystrophic phenotype. To test this, we treated C57BL10 and mdx mice with vehicle (V) or 6‐hydroxydopamine (6‐OHDA; 250 mg/kg, sc, on postnatal day 4, 6, 8, 10, 12) to selectively destroy peripheral sympathetic nerves. Hindlimb and diaphragm muscles were removed from 10–12 wk old mice and evaluated for dystrophic pathology. In C57BL10 mice, 6‐OHDA had no effect on muscle histopathology. In mdx mice, 6‐OHDA significantly reduced the number of fibers with centralized nuclei by 15% in gastrocnemius and by 25% in diaphragm (P<0.05 vs V). 6‐OHDA also significantly reduced collagen infiltration by 61% in gastrocnemius and by 33% in diaphragm (P<0.05 vs V). Findings were similar in mdx mice treated with prazosin (10 mg/kg/d, po, starting at 4 wk) to block α 1 ‐adrenoceptors. These data demonstrate that the dystrophic phenotype of hindlimb and diaphragm muscles of mdx mice is amenable to treatment with sympatholytics, suggesting a role for sympathetic nerves in the pathogenesis of muscular dystrophy. Supported by NIH AR051034.