Abstract

Amyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared with the corresponding ALS untrained groups and normalized to the wild-type group. Enzyme activity and protein content were analyzed in the spinal cord homogenates. The results show autophagy disruptions causing accumulation of p62 accompanied by low PGC-1α and IGF-1 content in the spinal cord of SOD1-G93A mice. Swim training triggered a neuroprotective effect, attenuation of NF-l degradation, less accumulated p62, and lower autophagy initiation. The IGF-1 pathway induces pathophysiological adaptation to maintain energy demands through anaerobic metabolism and mitochondrial protection.

Graphical Abstract

Key messages

• The increased protein content of p62 in the spinal cord of SOD1-G93A mice suggests that autophagic clearance and transportation are disrupted.

• Swim training attenuates neurofilament light destruction in the spinal cord of SOD1-G93A mice.

• Swim training reducing OGDH provokes suppression of ATP-consuming anabolic pathways. Swim training induces energy metabolic changes and mitochondria protection through the IGF-1 signaling pathway.

中文翻译：

---

SOD1-G93A 小鼠游泳训练改变脊髓异常自噬和线粒体能量代谢

摘要

肌萎缩侧索硬化症 (ALS) 可能是由多种机制功能障碍引起的，例如蛋白质积累、线粒体自噬和线粒体生物发生。该研究的目的是评估 ALS 发展的分子机制以及游泳训练对这些过程的影响。在本研究中，使用 ALS 动物模型 SOD1-G93A 小鼠，并以野生型小鼠作为对照。小鼠每周游泳 5 次，每次 30 分钟。在 ALS 发病前（70 天大）、ALS 1 疾病发病时（116 天大）和 ALS 疾病末期（130 天大）对小鼠进行分析，并与相应的 ALS 未训练组进行比较，并标准化为野生型组。分析脊髓匀浆中的酶活性和蛋白质含量。结果显示，自噬破坏导致 SOD1-G93A 小鼠脊髓中 p62 积聚，并伴有低 PGC-1α 和 IGF-1 含量。游泳训练引发了神经保护作用、NF-1 降解减弱、p62 积累减少和自噬启动降低。IGF-1 途径诱导病理生理适应，通过无氧代谢和线粒体保护维持能量需求。

图形概要

关键信息

• SOD1-G93A 小鼠脊髓中 p62 蛋白含量的增加表明自噬清除和运输被破坏。

• 游泳训练可减轻 SOD1-G93A 小鼠脊髓中的神经丝光破坏。

• 减少 OGDH 的游泳训练会抑制消耗 ATP 的合成代谢途径。游泳训练通过 IGF-1 信号通路诱导能量代谢变化和线粒体保护。