Molecular mechanisms underlying the positive role of treadmill training in locomotor recovery after spinal cord injury

Objectives: This study aimed to investigate the molecular mechanisms underlying the positive role of treadmill training (TMT) in locomotor recovery. Methods: GSE52763 microarray data were downloaded from GEO database, which was collected from the lumbar spinal cord samples of three groups of mice: mice subjected to contusive injury and killed 1 week after injury (I1), mice subjected to injury and killed 3 weeks after injury (I3), and mice subjected to injury and TMT beginning at week 1 and lasting until week 3 (T3). Differential expression analysis between I3 and I1, between T3 and I1 and between T3 and I3 were performed by T-test using R/LIMMA. Genes with | log(2)FC (fold change)| > 0.58 and P-value < 0.05 were considered as differentially expressed genes (DEGs). Specific I3 vs I1 DEGs and T3 vs I1 DEGs were screened. Then TMT-induced specific DEGs were subject to functional and pathway enrichment analysis using DAVID online tool. Protein-protein interaction (PPI) analysis was also carried out using the STRING database. Results: Finally, 82 upregulated DEGs and 297 downregulated DEGs were found specifically induced by TMT. Specific upregulated DEGs were mostly enriched in response to organic substance and morphogenesis-related events, and specific downregulated DEGs were related to positive regulation of transcription. ATP2A1, PRKACA, ITPR2 and so on had high connection degree in the PPI network of the specific upregulated DEGs; FOS, GSK3B and so on had high degrees in the PPI network of the specific downregulated DEGs. Conclusion: ATP2A1, C-FOS and GSK3B may have critical roles in the positive role of TMT in locomotor recovery.