Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, Bazynskiego 8, 80-309, Gdansk, Poland.
Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.
J Mol Med (Berl). 2024 Mar;102(3):379-390. doi: 10.1007/s00109-023-02410-8. Epub 2024 Jan 10.
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. 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.
肌萎缩侧索硬化症（ALS）可能是由于蛋白质积累、线粒体自噬和生物发生等各种机制的功能障碍引起的。本研究的目的是评估 ALS 发展中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 SOD1-G93A 小鼠作为 ALS 动物模型，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 天龄）、发病时（116 天龄）和疾病终末期（130 天龄）对小鼠进行分析，并与相应的未训练 ALS 组和野生型组进行比较。分析脊髓匀浆中的酶活性和蛋白质含量。结果显示，SOD1-G93A 小鼠脊髓中的自噬破坏导致 p62 积累，同时 PGC-1α 和 IGF-1 含量降低。游泳训练引发了神经保护作用，NF-l 降解减弱，p62 积累减少，自噬起始降低。IGF-1 通路通过无氧代谢和线粒体保护诱导病理生理适应，以维持能量需求。主要结论：SOD1-G93A 小鼠脊髓中 p62 蛋白含量增加表明自噬清除和转运受到破坏。游泳训练可减轻 SOD1-G93A 小鼠脊髓中神经丝轻链的破坏。游泳训练减少 OGDH 可抑制 ATP 消耗性合成代谢途径。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。
