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

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shaotian Zhang, Huihui Zou, Xiaopei Zou, Jiaqia Ke, Bofang Zheng, Xinrun Chen, Xianju Zhou, Jiana Wei
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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.

Abstract Image

低频重复经颅磁刺激治疗癫痫持续状态小鼠CeRNA网络构建的转录组测序
近年来,重复经颅磁刺激(rTMS)治疗神经和精神疾病取得了很大进展。本研究旨在探讨rTMS如何通过调控lncRNA-miRNA-mRNA的竞争性内源性rna (ceRNAs)发挥其治疗作用。采用高通量测序方法分析了低频rTMS (LF-rTMS)和假性rTMS两种治疗方式对雄性癫痫持续状态(SE)小鼠的lncRNA、miRNA和mRNA表达的差异。进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)途径富集分析。建立基因-基因交叉连锁网络;筛选出关键基因。采用qRT-PCR验证基因-基因相互作用。我们的研究结果显示,LF-rTMS组与sham rTMS组之间有1615个lncrna、510个mrna和17个mirna的表达差异。微阵列检测这些lncrna、mrna和mirna的表达差异与qPCR结果一致。氧化石墨烯功能富集表明,免疫相关的分子机制、生物学过程和GABA-A受体活性在LF-rTMS处理的SE小鼠中发挥了作用。KEGG通路富集分析显示,差异表达基因与T细胞受体信号通路、原发性免疫缺陷和Th17细胞分化信号通路相关。基于Pearson相关系数和miRNA建立基因-基因交叉连锁网络。综上所述,LF-rTMS通过调节GABA-A受体活性传递、改善免疫功能和生物学过程来缓解SE,提示LF-rTMS治疗癫痫的潜在ceRNA分子机制。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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