Transcriptome Sequencing of CeRNA Network Constructing in Status Epilepticus Mice Treated by Low-Frequency Repetitive Transcranial Magnetic Stimulation

J Mol Neurosci. 2023 May;73(4-5):316-326. doi: 10.1007/s12031-023-02108-z. Epub 2023 May 3.

Abstract

It is shown that great progress was recently made in the treatment of repetitive transcranial magnetic stimulation (rTMS) for neurological and psychiatric diseases. This study aimed to address how rTMS exerted it therapeutic effects by regulating competitive endogenous RNAs (ceRNAs) of lncRNA-miRNA-mRNA. The distinction of lncRNA, miRNA and mRNA expression in male status epilepticus (SE) mice treated by two different ways, low-frequency rTMS (LF-rTMS) vs. sham rTMS, was analyzed by high-throughput sequencing. The Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Gene-Gene Cross Linkage Network was established; pivotal genes were screened out. qRT-PCR was used to verify gene-gene interactions. Our results showed that there were 1615 lncRNAs, 510 mRNAs, and 17 miRNAs differentially which were expressed between the LF-rTMS group and the sham rTMS group. The expression difference of these lncRNAs, mRNAs, and miRNAs by microarray detection were consistent with the results by qPCR. GO functional enrichment showed that immune-associated molecular mechanisms, biological processes, and GABA-A receptor activity played a role in SE mice treated with LF-rTMS. KEGG pathway enrichment analysis revealed that differentially expressed genes were correlated to T cell receptor signaling pathway, primary immune deficiency and Th17 cell differentiation signaling pathway. Gene-gene cross linkage network was established on the basis of Pearson's correlation coefficient and miRNA. In conclusion, LF-rTMS alleviates SE through regulating the GABA-A receptor activity transmission, improving immune functions, and biological processes, suggesting the underlying ceRNA molecular mechanisms of LF-rTMS treatment for epilepsy.

Keywords: CeRNAs; Interaction network; LncRNA; Low-frequency rTMS; MiRNA; Status epilepticus; Transcriptome sequencing.

MeSH terms

  • Animals
  • Gene Regulatory Networks
  • Male
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, GABA-A / genetics
  • Status Epilepticus* / genetics
  • Status Epilepticus* / therapy
  • Transcranial Magnetic Stimulation
  • Transcriptome

Substances

  • RNA, Long Noncoding
  • Receptors, GABA-A
  • MicroRNAs
  • RNA, Messenger