| BackgroundRepetitive transcranial magnetic stimulation(rTMS)is a non-invasive neuroelectrophysiological technique that uses the principle of electromagnetic induction to generate a magnetic field,induces cells to generate induced currents,and causes neurons to inhibit or excite.Now it has been widely used in the treatment of neuropsychiatric diseases since its introduction.However,the current therapeutic mechanism of rTMS remains unclear,and there is a lack of biological indicators for evaluating the sensitivity of treatment for the clinical application of rTMS.ObjectivesTo investigate the effects of rTMS intervention effects on gene expression profiles in hippocampus and frontal lobe in rats.The differentially expressed genes were obtained.By analyzing the differentially expressed genes and the enrichment pathways to predict the biological indicators of rTMS treatment sensitivity.Methods1.Normal SD rats were randomly divided into normal control group and rTMS group.The rats in rTMS group were intervened by magnetic stimulator.Three courses of treatment lasted for three weeks.2.The differentially expressed genes of two groups were obtained by RNA-seq technology and then were performed into cluster analysis.3.The functions and Kyoto Encyclopedia of Genesand Genomes(KEGG)pathways of differentially expressed genes were mapped in Gene Ontology(GO)and KEGG pathway database.4.The transcriptome sequencing results were detected by Quantitative Real-time polymerase chain reaction(RT-PCR).5.Use statistical software SPSS19.0 and Independent-sample t test to analyze experimental data.Inspection level ?=0.05.Results1.Compared to the normal control group,367 differentially expressed genes were screened in hippocampus,70 up-regulated genes and 297 down-regulated genes.And 401 differentially expressed genes were screened in frontal,359 up-regulated genes and 42 down-regulated genes.2.According to GO enrichment classification,the above differentially expressed genes in rat hippocampus mainly involve the following biological functions: oxygen transport,cell adhesion,potassium ion transmembrane transport,hippo signaling,exocyst,bicellular tight junction,insulin-like growth factor binding,fibroblast growth factor receptor binding,etc.The differentially expressed genes in rat frontal lobe mainly involve the following biological functions: positive regulation of transcription of DNA-templated,positive regulation of transcription from RNA polymerase promoter,extracellular matrix,receptor complex,transcription factor activity of sequence-specific DNA binding,DNA binding.3.KEGG enrichment analysis showed that the differentially expressed genes in hippocampus were mainly concentrated in Pathways in cancer,PI3K-Akt signaling pathway,cholinergic synapse,GABA synapse,Signaling pathways regulating pluripotency of stem cells,cell adhesion molecules,Hippo signaling pathway,longevity regulation pathway,Focal adhesion,ECM-receptor interaction and other signaling pathways.The differentially expressed genes in frontal lobe were mainly enriched in ECM-receptor interaction,Focal adhesion,protein digestion and absorption,MicroRNAs in cancer,PI3K-Akt signaling pathway,Signaling pathways regulating pluripotency of stem cells,TGF-beta signaling pathway,Hippo signaling pathway,Longevity regulating pathway-mammal,cGMP-PKG signaling pathway,mTOR signaling pathway and so on.The differentially expressed genes in hippocampus and frontal lobe are CO-enriched in PI3K-Akt signaling pathway,regulation of stem cell pluripotent signaling pathway,focal adhesion,ECM-receptor interaction and Hippo signaling pathway.4.There are part of differentially expressed genes verified by real-time quantitative PCR were consistent with transcriptome results.Conclusions1.Transcriptome sequencing analysis showed that rTMS intervention can induce changes in gene expression profiles in multiple brain regions of rats,and rTMS-induced gene expression changes are an important part of their physiological functions.2.The KEGG pathway analysis of differentially expressed genes showed that rTMS can induce the expression changes of multiple gene pathways in rat brain.These pathway functions are related to biological processes such as regulating cell proliferation and apoptosis,mediating cell-to-cell signaling,and participating in cell differentiation and regeneration,suggesting that the effect of rTMS on rat gene expression profile is a systematic biological change. |
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