Cavanaugh Catherine Anne, Moore Amanda E, Fitz Nicholas Francis, Lefterov Iliya, Koldamova Radosveta
bioRxiv. 2025 Jul 27:2025.07.25.666815. doi: 10.1101/2025.07.25.666815.
Neuromuscular electrical stimulation (NMES) was 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 anterior muscle, brain, and plasma-derived EVs following NMES of WT and Klotho heterozygous (Kl ). 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 non-coding RNA transcriptome of plasma EVs with functional patterns suggesting response to oxygen and insulin, and long-term synaptic potentiation. Brain transcriptome showed little functional overlap between WT and Kl mice. In WT, brain upregulation of genes were related to blood flow and cell adhesion processes while Kl shows upregulation of immune function. 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klotho杂合子（Kl ）小鼠在接受NMES后，胫骨前肌、大脑和血浆来源的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都与葡萄糖代谢和对胰岛素的反应有关，且各基因型中受影响的途径具有独特性。血浆EVs的非编码RNA转录组与提示对氧气和胰岛素反应以及长期突触增强的功能模式存在相似性。大脑转录组显示WT和Kl 小鼠之间几乎没有功能重叠。在WT小鼠中，大脑中基因的上调与血流和细胞黏附过程有关，而Kl 小鼠则显示免疫功能上调。结果表明，相似的代谢功能在刺激部位受到影响，但刺激对大脑的远端影响与klotho缺乏有关。
