High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats
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...
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| Veröffentlicht in: | Neurochemical research 2021-02, Vol.46 (2), p.276-286 |
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| creator | Hong, Jiena Chen, Jiemei Li, Chao An, Delian Tang, Zhiming Wen, Hongmei |
| description | 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. |
| doi_str_mv | 10.1007/s11064-020-03161-5 |
| format | Article |
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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.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-020-03161-5</identifier><identifier>PMID: 33136229</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biochemistry ; Bioinformatics ; Biomedical and Life Sciences ; Biomedicine ; Brain Ischemia - genetics ; Brain Ischemia - metabolism ; Brain Ischemia - therapy ; Cell Biology ; Cerebral blood flow ; Cognition - physiology ; Cognitive ability ; Complications ; Encyclopedias ; Functional plasticity ; Gene Expression - physiology ; Gene Ontology ; Gene sequencing ; Genes ; Genomes ; Glutamatergic transmission ; Hippocampus ; Hippocampus - metabolism ; Infarction, Middle Cerebral Artery - genetics ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - therapy ; Ischemia ; Magnetic fields ; Male ; Morris Water Maze Test - physiology ; Network analysis ; Neurochemistry ; Neurology ; Neuronal Plasticity - physiology ; Neurosciences ; Occlusion ; Original Paper ; Plasticity ; Potassium channels ; Protein interaction ; Protein Interaction Maps ; Proteins ; Rats ; Rats, Sprague-Dawley ; Ribonucleic acid ; RNA ; Stroke ; Synapses ; Synaptic plasticity ; Synaptic transmission ; Transcranial Magnetic Stimulation</subject><ispartof>Neurochemical research, 2021-02, Vol.46 (2), p.276-286</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-794bc3c2daf8ecc2717a499584ff30759b453dcbd72a1e7f1a30cea4bff6c32b3</citedby><cites>FETCH-LOGICAL-c375t-794bc3c2daf8ecc2717a499584ff30759b453dcbd72a1e7f1a30cea4bff6c32b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-020-03161-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-020-03161-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33136229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, Jiena</creatorcontrib><creatorcontrib>Chen, Jiemei</creatorcontrib><creatorcontrib>Li, Chao</creatorcontrib><creatorcontrib>An, Delian</creatorcontrib><creatorcontrib>Tang, Zhiming</creatorcontrib><creatorcontrib>Wen, Hongmei</creatorcontrib><title>High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>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.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain Ischemia - genetics</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - therapy</subject><subject>Cell Biology</subject><subject>Cerebral blood flow</subject><subject>Cognition - physiology</subject><subject>Cognitive ability</subject><subject>Complications</subject><subject>Encyclopedias</subject><subject>Functional plasticity</subject><subject>Gene Expression - physiology</subject><subject>Gene Ontology</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genomes</subject><subject>Glutamatergic transmission</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Infarction, Middle Cerebral Artery - genetics</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - therapy</subject><subject>Ischemia</subject><subject>Magnetic fields</subject><subject>Male</subject><subject>Morris Water Maze Test - physiology</subject><subject>Network analysis</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neuronal Plasticity - physiology</subject><subject>Neurosciences</subject><subject>Occlusion</subject><subject>Original Paper</subject><subject>Plasticity</subject><subject>Potassium channels</subject><subject>Protein interaction</subject><subject>Protein Interaction Maps</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Stroke</subject><subject>Synapses</subject><subject>Synaptic plasticity</subject><subject>Synaptic transmission</subject><subject>Transcranial Magnetic Stimulation</subject><issn>0364-3190</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUtP3DAUha2qVRkef4AFstQNm7S2bxwny2rEwEhUIB5ry_HcBNPEmdrJSPn3NQxtpS5Y3cX5zrHvPYSccvaVM6a-Rc5ZkWdMsIwBL3gmP5AFlwqyomLwkSwYJBl4xQ7IYYzPjCWb4J_JAQCHQohqQX5eufYpWwX8NaG3Mw0PP-7put-GYYeRLofWu9HtkK4mb0c3eFrP9A7bqTOj8y29n73Zjs7S287ENN04U-fpEgPWwXR0He0T9km_M2M8Jp8a00U8eZtH5HF18bC8yq5vLtfL79eZBSXHTFV5bcGKjWlKtFYorkxeVbLMmwaYklWdS9jYeqOE4agaboBZNHndNIUFUcMROd_npi3SWnHUvYsWu854HKaoRS6LsmCqLBL65T_0eZiCT79LVClB5JVQiRJ7yoYhxoCN3gbXmzBrzvRLFXpfhU5V6NcqtEyms7foqe5x89fy5_YJgD0Qk-RbDP_efif2Nx5llJ0</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Hong, Jiena</creator><creator>Chen, Jiemei</creator><creator>Li, Chao</creator><creator>An, Delian</creator><creator>Tang, Zhiming</creator><creator>Wen, Hongmei</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20210201</creationdate><title>High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats</title><author>Hong, Jiena ; Chen, Jiemei ; Li, Chao ; An, Delian ; Tang, Zhiming ; Wen, Hongmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-794bc3c2daf8ecc2717a499584ff30759b453dcbd72a1e7f1a30cea4bff6c32b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain Ischemia - genetics</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - therapy</topic><topic>Cell Biology</topic><topic>Cerebral blood flow</topic><topic>Cognition - physiology</topic><topic>Cognitive ability</topic><topic>Complications</topic><topic>Encyclopedias</topic><topic>Functional plasticity</topic><topic>Gene Expression - physiology</topic><topic>Gene Ontology</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genomes</topic><topic>Glutamatergic transmission</topic><topic>Hippocampus</topic><topic>Hippocampus - metabolism</topic><topic>Infarction, Middle Cerebral Artery - genetics</topic><topic>Infarction, Middle Cerebral Artery - metabolism</topic><topic>Infarction, Middle Cerebral Artery - therapy</topic><topic>Ischemia</topic><topic>Magnetic fields</topic><topic>Male</topic><topic>Morris Water Maze Test - physiology</topic><topic>Network analysis</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neuronal Plasticity - physiology</topic><topic>Neurosciences</topic><topic>Occlusion</topic><topic>Original Paper</topic><topic>Plasticity</topic><topic>Potassium channels</topic><topic>Protein interaction</topic><topic>Protein Interaction Maps</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Stroke</topic><topic>Synapses</topic><topic>Synaptic plasticity</topic><topic>Synaptic transmission</topic><topic>Transcranial Magnetic Stimulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Jiena</creatorcontrib><creatorcontrib>Chen, Jiemei</creatorcontrib><creatorcontrib>Li, Chao</creatorcontrib><creatorcontrib>An, Delian</creatorcontrib><creatorcontrib>Tang, Zhiming</creatorcontrib><creatorcontrib>Wen, Hongmei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Jiena</au><au>Chen, Jiemei</au><au>Li, Chao</au><au>An, Delian</au><au>Tang, Zhiming</au><au>Wen, Hongmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>46</volume><issue>2</issue><spage>276</spage><epage>286</epage><pages>276-286</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33136229</pmid><doi>10.1007/s11064-020-03161-5</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Biochemistry Bioinformatics Biomedical and Life Sciences Biomedicine Brain Ischemia - genetics Brain Ischemia - metabolism Brain Ischemia - therapy Cell Biology Cerebral blood flow Cognition - physiology Cognitive ability Complications Encyclopedias Functional plasticity Gene Expression - physiology Gene Ontology Gene sequencing Genes Genomes Glutamatergic transmission Hippocampus Hippocampus - metabolism Infarction, Middle Cerebral Artery - genetics Infarction, Middle Cerebral Artery - metabolism Infarction, Middle Cerebral Artery - therapy Ischemia Magnetic fields Male Morris Water Maze Test - physiology Network analysis Neurochemistry Neurology Neuronal Plasticity - physiology Neurosciences Occlusion Original Paper Plasticity Potassium channels Protein interaction Protein Interaction Maps Proteins Rats Rats, Sprague-Dawley Ribonucleic acid RNA Stroke Synapses Synaptic plasticity Synaptic transmission Transcranial Magnetic Stimulation |
| title | High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats |
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