Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
University California, Los Angeles, School of Dentistry, Section of Biosystems and Function, Laboratory of Neuropharmacology, 714 Tiverton Los Angeles, CA 90095, United States.
Sci Rep. 2024 Oct 16;14(1):24279. doi: 10.1038/s41598-024-74669-x.
Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages. Our analysis showed that, unlike limb muscles, masticatory muscles retain their normal structure and cell makeup throughout most of the disease course. We found an increase in the number of muscle satellite cells (SCs), which are essential for muscle repair, in masticatory muscles. In addition, we observed no reduction in the number of muscle nuclei and no muscle fibre-type switching in masticatory muscles. This indicates that masticatory muscles have a higher resistance to ALS-related damage than limb muscles, likely because of differences in cell composition and repair mechanisms. Understanding why masticatory muscles are less affected by ALS could lead to the development of new treatments. This study highlights the importance of studying different muscle groups in ALS to clarify disease aetiology and mechanisms.
肌萎缩侧索硬化症(ALS)逐渐损害运动神经元,导致肌肉无力和随意肌肉控制丧失。本研究比较了 ALS 模型小鼠从疾病发病到死亡时 SOD1 突变对咀嚼肌和四肢肌肉的影响。值得注意的是,类似于 ALS 的表型出现后不久,四肢肌肉开始萎缩,而咀嚼肌在后期仍保持其体积和功能。我们的分析表明,与四肢肌肉不同,咀嚼肌在疾病过程的大部分时间内保持正常的结构和细胞组成。我们发现咀嚼肌中的肌肉卫星细胞(SCs)数量增加,SCs 对于肌肉修复至关重要。此外,我们观察到咀嚼肌中的肌肉细胞核数量没有减少,也没有发生肌肉纤维类型转换。这表明咀嚼肌对 ALS 相关损伤的抵抗力高于四肢肌肉,这可能是由于细胞组成和修复机制的差异。了解咀嚼肌为何受 ALS 的影响较小,可能会促使开发新的治疗方法。本研究强调了在 ALS 中研究不同肌肉群的重要性,以阐明疾病的病因和机制。