This study investigates changes with respect to increasing protein levels in dystrophic nerves of two mdx mouse models of Duchenne muscular dystrophy (DMD). We propose that these nerve changes result from progressive ongoing damage to neuromuscular junctions (NMJs) due to repeated intrinsic bouts of necrosis in dystrophic muscles. We compared sciatic nerves from classic mdx mice aged 13, 15 and 18 months (M), with D2.mdx mice (on DBA2 background) aged 9 and 13 M, using immunoblotting to quantify levels of 7 proteins. The neuronal proteins S100β and Tau5 were increased by 13 M in mdx nerves (compared with WT), indicating ongoing myonecrosis in this strain. In striking contrast there was no difference in levels of these neuronal proteins for D2.mdx and D2.WT sciatic nerves at 13 M, indicating reduced myonecrosis over this time in D2.mdx mice compared with mdx. These novel changes in mdx sciatic nerves by 13 M, suggest early denervation or neurodegeneration of dystrophic nerves that is likely irreversible and progressive. This neuronal readout of persistent myonecrosis may provide a useful new long-term biomarker for preclinical studies that aim to reduce myonecrosis, plus such neuronal changes present potential new drug targets to help maintain the function of DMD muscles.

这项研究调查了增加的杜兴氏肌营养不良症（DMD）的两种mdx小鼠模型的营养不良神经中蛋白质水平的变化。我们提出，这些神经变化是由于营养不良性肌肉反复内在坏死而对神经肌肉接头（NMJs）进行性进行性损伤所致。我们将年龄分别为13、15和18个月（M）的经典mdx小鼠的坐骨神经与D2进行了比较。使用免疫印迹法定量7种蛋白质的9和13 M年龄的mdx小鼠（在DBA2背景下）。在mdx中神经元蛋白S100β和Tau5增加了13 M神经（与WT相比），表明该菌株中持续发生坏死。形成鲜明对比的是，D2的这些神经元蛋白水平没有差异。mdx和D2.WT坐骨神经在13 M处，表明在这段时间内D2中的骨髓坏死减少。mdx小鼠与mdx的比较。mdx坐骨神经的这些新变化达13 M，表明营养不良性神经的早期失神经或神经退行性变可能是不可逆的和进行性的。持续性肌坏死的这种神经元读数可能为临床前研究提供有用的新的长期生物标志物，旨在减少肌坏死，此外，这种神经元变化也代表了潜在的新药物靶标，有助于维持DMD肌肉的功能。