Transcriptomic Responses to Neuromuscular Electrical Stimulation (NMES) in Muscle, Brain and Plasma Exosomes in WT and Klotho Deficient Mice [mRNA]

Previous studies indicate extracellular vesicles (EVs) play a role in cellular communication which may be impacted by neuromuscular electrical stimulation (NMES), a noninvasive approach to improve daily living and functional motor activities. Therefore, we utilized NMES to stimulate the tibialis anterior of WT and KlHET mice and evaluated transcriptomic profiles of muscle tissue, brain tissue, and plasma-derived EVs. Muscle mRNA indicate that genes related to metabolic processes are upregulated in response to NMES in but have little overlap in WT and KlHET NMES versus control. Brain mRNA in WT shows upregulation of several genes related to blood flow and cell adhesion processes while KlHET shows downregulation in cell adhesion processes and immune function. In plasma-derived EVs, little overlap in ncRNA, with the exception of let-7d-5p which regulates insulin signaling targets and immune responses, was present. Findings indicate local and distal transcriptomic metabolic effects of NMES are mediated by KLOTHO deficiency.