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Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors
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Neuronal hyperexcitability is a phenomenon associated with early Alzheimer's disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10037419"> <a href="/gui2/?type=authors&mode=browse&sel=10037419" target="_blank">Varga, E</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10063613"> <a href="/gui2/?type=authors&mode=browse&sel=10063613" target="_blank">Juhasz, G</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10011919"> <a href="/gui2/?type=authors&mode=browse&sel=10011919" target="_blank">Bozso, Z</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000481"> <a href="/gui2/?type=authors&mode=browse&sel=10000481" target="_blank">Penke, B</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000567"> <a href="/gui2/?type=authors&mode=browse&sel=10000567" target="_blank">Fulop, L</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10027696"> <a href="/gui2/?type=authors&mode=browse&sel=10027696" target="_blank">Szegedi, V ✉</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;2755870" mtid="2755870" target="_blank">Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors</a></div> <div class="pub-info"> <span class="journal-title">NEURAL PLASTICITY</span> <span class="journal-volume">2014</span> <span class="page"> Paper: 584314 , 12 p. </span> <span class="year">(2014)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1155/2014/584314" target="_blank" href="https://doi.org/10.1155/2014/584314"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000344264700001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000344264700001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84925376428" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84925376428"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="25276438" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25276438&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="10503" target="_blank" href="http://publicatio.bibl.u-szeged.hu/10503"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="deleted-record">Zárolt</span> <span class="short-pub-mtid"> Közlemény:2755870 </span> <span class="status-holder"><span class="status-data status-ADMIN_APPROVED"> Admin láttamozott </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 22</span> | Független: 21 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 22 | Scopus jelölt: 21 | WoS/Scopus jelölt: 22 | DOI jelölt: 22 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10037419"><a href="/gui2/?type=authors&mode=browse&sel=10037419" target="_blank">Varga E (<span class="authorship-author-name">Varga Edina</span> <span class="authorAux-mtmt"> Idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span> ; <span class="author-name" mtid="10063613"><a href="/gui2/?type=authors&mode=browse&sel=10063613" target="_blank">Juhasz G (<span class="authorship-author-name">Juhász Gábor</span> <span class="authorAux-mtmt"> elektofiziológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span> ; <span class="author-name" mtid="10011919"><a href="/gui2/?type=authors&mode=browse&sel=10011919" target="_blank">Bozso Z (<span class="authorship-author-name">Bozsó Zsolt</span> <span class="authorAux-mtmt"> Peptidkémia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span> ; <span class="author-name" mtid="10000481"><a href="/gui2/?type=authors&mode=browse&sel=10000481" target="_blank">Penke B (<span class="authorship-author-name">Penke Botond</span> <span class="authorAux-mtmt"> Neurodegeneráció, peptidkémia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span> ; <span class="author-name" mtid="10000567"><a href="/gui2/?type=authors&mode=browse&sel=10000567" target="_blank">Fulop L (<span class="authorship-author-name">Fülöp Lívia</span> <span class="authorAux-mtmt"> Neurodegeneratív betegségekkel kapcsolatos gyóg...</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Orvosi Vegytani Intézet</span> ; <span class="author-name" mtid="10027696"><a href="/gui2/?type=authors&mode=browse&sel=10027696" target="_blank">Szegedi V ✉ (<span class="authorship-author-name">Szegedi Viktor</span> <span class="authorAux-mtmt"> Idegtudomány</span>) </a> </span> <span class="author-affil"><span title="MTA Szegedi Biológiai Kutatóközpont">MTA SZBK</span>/Biokémiai Intézet</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse¶ms=publication;2755870" target="_blank">Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors</a></div> <div> <span class="journal-title">NEURAL PLASTICITY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/2090-5904">2090-5904</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1687-5443">1687-5443</a>)</span>: <span class="journal-volume">2014</span> <span class="page"> Paper 584314. 12 p. </span> <span class="year">(2014)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1155/2014/584314" target="_blank" href="https://doi.org/10.1155/2014/584314"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000344264700001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000344264700001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84925376428" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84925376428"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="25276438" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=25276438&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="10503" target="_blank" href="http://publicatio.bibl.u-szeged.hu/10503"> SZTE Publicatio </a> </span> </span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 22</span> | Független: 21 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 22 | Scopus jelölt: 21 | WoS/Scopus jelölt: 22 | DOI jelölt: 22 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;2755870&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 5 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 2755870</span> | <span class="status-data status-ADMIN_APPROVED"> Admin láttamozott </span> <span class="oldId">Régi azonosító: 2755870</span> | Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="lastModified">Utolsó módosítás: 2024.02.27. 22:36 Pécsi Éva (MTMT Közp 3, admin) </div> <div class="lockedBy">Ideiglenesen zárolva 2024.03.11. 18:47 Pécsi Éva (MTMT Közp 3, admin) </div> </div></div>