Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator‐activated receptor gamma coactivator 1 alpha

Abstract 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.