METHODS: In this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in three sessions per week of running 20 cm/s for 20 min. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared with those of respective sedentary mice. For all the groups, force measurement, muscle histology, and molecular analyses were conducted.
RESULTS: Following the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates in both tibialis anterior (+24%, **P = 0.0026) and gastrocnemius (+18%, ****P < 0.0001) as well as enhanced collagen deposition (+20%, **P = 0.0064 in the tibialis anterior; +35%, **P = 0.0042 in the gastrocnemius) in the exercised A17 OPMD mice. In the supraphysiological resistance overload protocol, we also observed an increased collagen deposition (×2, ****P < 0.0001) in the plantaris muscle of A17 OPMD mice which was associated with larger muscle mass (×2, ****P < 0.0001) and fibre cross sectional area (×2, ***P = 0.0007) and increased absolute maximal force (×2, ****P < 0.0001) as well as a reduction in PABPN1 aggregate number (-16%, ****P < 0.0001).
CONCLUSIONS: Running exercise and mechanical overload led to very different outcome in skeletal muscles of A17 mice. Both types of exercise enhanced collagen deposition but while the running protocol increased aggregates, the OVL reduced them. More importantly OVL reversed muscle atrophy and maximal force in the A17 mice. Our study performed in a relevant model gives an indication of the effect of different types of exercise on OPMD muscle which should be further evaluated in humans for future recommendations as a part of the lifestyle of individuals with OPMD.
方法:在本研究中,我们测试了两种锻炼方案。在第一,基于耐力锻炼,FvB(野生型)和A17(OPMD)小鼠接受了为期6周的电动跑步机方案,包括每周3次20cm/s的跑步20分钟。在第二个协议中,基于慢性机械过载(OVL)产生的阻力运动,手术切除腓肠肌和比目鱼肌,诱导膈肌肥大。在这两种运动中,将A17和FvB小鼠的肌肉与久坐小鼠的肌肉进行比较。对于所有的团体,力测量,肌肉组织学,并进行了分子分析。
结果:遵循耐力锻炼方案,我们没有观察到肌肉生理参数的任何重大变化,但是胫骨前肌PABPN1核内聚集体的数量增加(+24%,**P=0.0026)和腓肠肌(+18%,****P<0.0001)以及增强的胶原蛋白沉积(+20%,**胫骨前肌P=0.0064;+35%,**在腓肠肌中P=0.0042)在锻炼的A17OPMD小鼠中。在超生理抗性过载方案中,我们还观察到A17OPMD小鼠的plant肌中胶原蛋白沉积增加(×2,*****P<0.0001),这与较大的肌肉质量(×2,*****P<0.0001)和纤维横截面积(×2,****P<0.0001)。
结论:跑步运动和机械超负荷导致A17小鼠骨骼肌的结果非常不同。两种类型的运动都增强了胶原蛋白的沉积,但是跑步方案增加了聚集体,OVL减少了他们。更重要的是,OVL逆转了A17小鼠的肌肉萎缩和最大力。我们在相关模型中进行的研究表明了不同类型的运动对OPMD肌肉的影响,应在人类中进一步评估,以作为OPMD个体生活方式的一部分。