Unilateral electrical stimulation of mice induces transcriptional response in stimulated leg with limited effect on non-stimulated contralateral leg

Abstract

Electrical stimulation is widely used to investigate localised muscle adaptations, with applications in both sports and rehabilitation. However, the systemic effects of electrical stimulation, particularly in the contralateral muscles that are not directly stimulated, are not well understood. This study investigated whether unilateral electrical stimulation induces transcriptional changes in both the electrically stimulated (ES) and non-stimulated (non-ES) contralateral legs, compared with the legs of sedentary control mice. RNA-sequence analysis revealed that 1320 and 55 genes were differentially expressed in the ES and non-ES, respectively, compared with controls using DEseq2 (false discovery rate cutoff = 0.05, minimal fold change = 1.5). Gene ontology and pathway enrichment analyses identified that the biological processes of immune response, muscle development, and response to stimuli were upregulated in the ES leg, while immune response and stress signalling were upregulated in the non-ES leg. Although the non-ES leg exhibited minimal transcriptional changes, Tbc1d1, which enhances glucose uptake, and Mss51, a regulator of mitochondrial function, were upregulated while Ddit4, a negative regulator of mammalian/mechanistic target of rapamycin signalling, and stress responsive protein Gadd45g were downregulated. These findings aid the understanding of molecular mechanisms underlying the cross-education effect and suggest that contralateral effects of electrical stimulation are limited, despite potential signalling across the legs.