期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 178, 期 1, 页码 273-283出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2010.11.027
关键词
-
类别
资金
- Lundbeck Foundation [R19-A2177]
- Big Lottery Fund [RA3/691]
- Medical Research Council UK through the Centre for Neuromuscular Diseases [G0601943]
- [RG/1/010136302]
- Medical Research Council [G0601943] Funding Source: researchfish
- MRC [G0601943] Funding Source: UKRI
The disease mechanisms underlying dystrophin-deficient muscular dystrophy are complex, involving not only muscle membrane fragility, but also dysregulated calcium homeostasis. Specifically, it has been proposed that calcium channels directly initiate a cascade of pathological events by allowing calcium ions to enter the cell. The objective of this study was to investigate the effect of chronically blocking calcium channels with the aminoglycoside antibiotic streptomycin from onset of disease in the mdx mouse model of Duchenne muscular dystrophy (DMD). Treatment in utero onwards delayed onset of dystrophic symptoms in the limb muscle of young mdx mice, but did not prevent degeneration and regeneration events occurring later in the disease course. Long-term treatment had a positive effect on limb muscle pathology, reduced fibrosis, increased sarcolemmal stability, and promoted muscle regeneration in older mice. However, streptomycin treatment did not show positive effects in diaphragm or heart muscle, and heart pathology was worsened. Thus, blocking calcium channels even before disease onset does not prevent dystrophy, making this an unlikely treatment for DMD. These findings highlight the importance of analyzing several time points throughout the life of the treated mice, as well as analyzing many tissues, to get a complete picture of treatment efficacy. (Am J Pathol 2011, 178:273-283; DOI: 10.1016/j.ajpath.2010.11.027)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据