Cavanaugh Catherine Anne, Moore Amanda E, Fitz Nicholas Francis, Lefterov Iliya, Koldamova Radosveta
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Int J Mol Sci. 2025 Aug 14;26(16):7849. doi: 10.3390/ijms26167849.
Neuromuscular electrical stimulation (NMES) has been shown to improve motor activities and daily living. Prior studies indicated extracellular vesicles (EVs) play a role in cellular communication. Here, we evaluated transcriptomic profiles of tibialis muscle, brain, and plasma-derived EVs following NMES in wild type (WT) and heterozygous (Kl) mice. Muscle RNA-seq data demonstrated that, in both genotypes, the most upregulated functional categories were related to glucose metabolism and response to insulin, with pathways uniquely affected in each genotype. There was a similarity of the non-coding RNA transcriptome of plasma EVs, with functional patterns suggesting response to oxygen and insulin and long-term synaptic potentiation. The brain transcriptome showed little functional overlap between WT and Kl mice. In WT, brain upregulation of genes was related to blood flow and cell adhesion processes, while Kl showed upregulation of immune function. The results indicate that similar metabolic function is impacted in the location of stimulation, but the distal impact of stimulation on the brain is associated with Klotho deficiency.
神经肌肉电刺激（NMES）已被证明可改善运动活动和日常生活能力。先前的研究表明，细胞外囊泡（EVs）在细胞通讯中发挥作用。在此，我们评估了野生型（WT）和杂合型（Kl）小鼠在接受NMES后，胫骨肌、脑以及血浆来源的EVs的转录组概况。肌肉RNA测序数据表明，在两种基因型中，上调最多的功能类别均与葡萄糖代谢和对胰岛素的反应有关，且各基因型中有独特受影响的通路。血浆EVs的非编码RNA转录组存在相似性，其功能模式表明对氧气和胰岛素有反应以及长期突触增强。脑转录组显示WT和Kl小鼠之间几乎没有功能重叠。在WT小鼠中，脑内基因的上调与血流和细胞粘附过程有关，而Kl小鼠则显示免疫功能上调。结果表明，刺激部位的代谢功能受到相似影响，但刺激对脑的远端影响与klotho缺乏有关。
