High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats
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ORIGINAL PAPER
High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats Jiena Hong1 · Jiemei Chen1 · Chao Li1 · Delian An1 · Zhiming Tang1 · Hongmei Wen1 Received: 28 September 2020 / Revised: 22 October 2020 / Accepted: 26 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Poststroke cognitive impairment (PSCI) is one of the most severe sequelae of stroke and lacks effective treatment. Previous studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) may be a promising PSCI therapeutic approach, but the underlying mechanism is unclear. To uncover the effect of rTMS on PSCI, a transient middle cerebral artery occlusion (tMCAO) model was established. Modified Neurological Severity Score (mNSS) test and Morris Water Maze (MWM) test were performed to assess the neurological and cognitive function of rats. Furthermore, to explore the underlying mechanism, differentially expressed genes (DEGs) in the hippocampus of rats in the rTMS group and tMCAO group were compared using RNA sequencing. Then, bioinformatics analysis, including gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, was conducted to elaborate these DEGs. Our results indicated that high-frequency rTMS could significantly improve neurological and cognitive function, according to mNSS and MWM tests. We found 85 DEGs, including 71 upregulated genes and 14 downregulated genes, between the rTMS group and tMCAO group. The major functional category was related to chemical synaptic transmission modulation and several DEGs were significantly upregulated in processes related to synaptic plasticity, such as glutamatergic synapses. Calb2, Zic1, Kcnk9, and Grin3a were notable in PPI analysis. These results demonstrate that rTMS has a beneficial effect on PSCI, and its mechanism may be related to the regulation of synaptic plasticity and functional genes such as Calb2, Zic1, Kcnk9, and Grin3a in the hippocampus. Keywords rTMS · Post stroke cognitive impairment · Synaptic plasticity · RNA sequencing · tMCAO
Jiena Hong and Jiemei Chen contributed equally to this work. * Hongmei Wen [email protected] Jiena Hong [email protected] Jiemei Chen [email protected] Chao Li [email protected] Delian An [email protected] Zhiming Tang [email protected] 1
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
Abbreviations rTMS Repetitive transcranial magnetic stimulation PSCI Poststroke cognitive impairment mNSS Modified Neurological Severity Score MWM Morris Water Maze DEGs Differentially expressed genes GO Gene ontology KEGG Kyoto Encyclopedia of Genes and Genomes PPI Protein-protein interactions RNA-seq RNA-sequencing tMCAO Transient middle cerebral artery occlusion BP Biological process CC Cellular component MF Molecular function SEM Standard error of means ANOVA Analys
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