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

作者全名："Su, Hong; Luo, Haodong; Wang, Yunhang; Zhao, Qin; Zhang, Qing; Zhu, Ying; Pan, Lu; Liu, Yuan; Yang, Ce; Yin, Ying; Tan, Botao"

作者地址："[Su, Hong; Luo, Haodong; Wang, Yunhang; Zhao, Qin; Zhang, Qing; Pan, Lu; Yin, Ying; Tan, Botao] Chongqing Med Univ, Dept Rehabil Med, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhu, Ying; Liu, Yuan; Yang, Ce] Army Med Ctr PLA, Inst Surg Res, Dept Special Environm War Wound Prevent & Treatmen, State Key Lab Trauma Burns & Combined Injuries, Chongqing, Peoples R China; [Yin, Ying; Tan, Botao] Chongqing Med Univ, Dept Rehabil Med, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing, Peoples R China"

通信作者："Yin, Y; Tan, BT (通讯作者)，Chongqing Med Univ, Dept Rehabil Med, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing, Peoples R China."

来源：GLIA

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001111058500001

JCR分区：Q1

影响因子：5.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：motor function; myelin repair; PGC1 alpha; spinal cord injury; treadmill training

摘要："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 (PGC1 alpha)-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 PGC1 alpha 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 PGC1 alpha knockdown in OLs was used to further unravel the role of PGC1 alpha 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 PGC1 alpha through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1 alpha, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair."

基金机构："the Chongqing Municipal Science and Technology Bureau and Health Commission; State Key Laboratory of Trauma, Burns and Combined Injuries of Army Medical Center of PLA"

基金资助正文："The authors thank the State Key Laboratory of Trauma, Burns and Combined Injuries of Army Medical Center of PLA for providing the experimental platform."