Institute of Neuroscience, Department of Clinical Neurophysiology, Uppsala University, 75185 Uppsala, Sweden.
Neurosci Res. 2013 Sep-Oct;77(1-2):102-9. doi: 10.1016/j.neures.2013.07.008. Epub 2013 Aug 7.
Myasthenia gravis (MG) patients with antibodies against muscle specific tyrosine kinase (MuSK+) typically present focal fatigue and atrophy of the facial and bulbar muscles, including the masseter muscle, whereas leg muscles often are clinically spared. This study addresses the regulation of the mTOR signaling pathway in the masseter muscle versus the leg muscle tibialis anterior (TA). We analyzed muscle morphology, protein levels of mTOR components as well as atrogenes and mitochondrial markers in these muscles of healthy control mice and mice with different clinical severity grades of MuSK+ experimental autoimmune MG (EAMG). Protein levels of mTOR components were reduced in the atrophic masseter muscle of MuSK+ EAMG mice, whereas enhanced accumulation of mTOR components was observed in the TA muscles. Two other muscles: omohyoid and soleus showed intermediate spectra. In conclusion, the anabolic mTOR signaling pathway is differentially regulated even in muscles with the same activity pattern in the same neuromuscular disease. This could in part explain the clinical phenotype in MuSK+ EAMG as well as in muscular dystrophies.
重症肌无力（MG）患者的肌肉特异性酪氨酸激酶（MuSK+）抗体通常表现为面部和球部肌肉（包括咬肌）的局灶性疲劳和萎缩，而腿部肌肉通常在临床上不受影响。本研究探讨了 mTOR 信号通路在咬肌与腿部胫骨前肌（TA）中的调节。我们分析了健康对照组小鼠和 MuSK+实验性自身免疫性重症肌无力（EAMG）不同临床严重程度级别的小鼠这些肌肉的肌肉形态、mTOR 成分的蛋白水平以及自噬基因和线粒体标志物。MuSK+EAMG 小鼠萎缩的咬肌中 mTOR 成分的蛋白水平降低，而 TA 肌肉中 mTOR 成分的积累增强。另外两块肌肉：胸锁乳突肌和比目鱼肌表现出中等谱。总之，即使在同一种神经肌肉疾病中具有相同活动模式的肌肉中，合成代谢 mTOR 信号通路也存在差异调节。这可以部分解释 MuSK+EAMG 以及肌肉营养不良症的临床表型。
