Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha
Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha
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作者：
Su，Hong;Luo，Haodong;Tan，Botao
越来越多的证据证明了体育锻炼对脊髓损伤（SCI）后髓鞘再生和运动功能表现的有效性。然而，跑台训练对脊髓损伤后髓鞘修复和功能恢复的分子机制尚未得到充分研究。在这里，我们探讨了跑台训练对上调过氧化物酶体增殖物激活受体γ共激活因子1 α（PGC1α）介导的髓鞘修复和胸部T10挫伤小鼠模型功能恢复的影响。对SCI小鼠进行为期4周的跑步机训练计划。采用免疫荧光、RNA荧光原位杂交和蛋白质印迹法检测少突胶质细胞生成相关蛋白和PGC1α的表达水平。透射电镜观察髓鞘结构。采用Basso小鼠量表（BMS）和CatWalk自动步态分析系统进行运动功能恢复评估。还确定了运动诱发电位（MEP）。此外，使用腺相关病毒（AAV）介导的OL中PGC1α敲低来进一步阐明PGC1α在运动诱导的髓鞘再生中的作用。我们发现跑步机训练促进少突胶质前体细胞（OPCs）增殖，增强少突胶质细胞（OLs）成熟，并增加髓鞘相关蛋白和髓鞘厚度，从而促进髓鞘修复和后肢功能表现以及SCI后神经传导的速度和幅度。此外，通过AAV下调PGC1α减弱了跑台训练的这些积极作用。总的来说，我们的研究结果表明，跑步机训练通过上调PGC1α来增强髓鞘再生和功能恢复，这应该为理解体育锻炼对髓鞘修复的影响提供了一个进步。
Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC1α)‐mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4‐week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis‐related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno‐associated virus (AAV)‐mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise‐induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin‐related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.