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Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?

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dc.contributor.authorCarvalho Rosa, José D.
dc.contributor.authorRodrigues, Nádia C.
dc.contributor.authorCruz, Armando
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorCunha-Reis, Diana
dc.date.accessioned2023-05-30T13:48:20Z
dc.date.available2023-05-30T13:48:20Z
dc.date.issued2023
dc.descriptionCopyright © 2023 Carvalho-Rosa, Rodrigues, Silva-Cruz, Vaz and Cunha-Reis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractNon-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity (EA) triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of EA were induced: (1) interictal-like EA evoked by Mg2+ withdrawal and K+ elevation to 6 mM in the superfusion medium or (2) ictal-like EA induced by bicuculline (10 μM). Both EA patterns induced and LTP-like effect on CA1 synaptic transmission prior to LTP induction. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA in synaptosomes isolated from these slices. EA enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser845 phosphorylation and the GluA1/GluA2 ratio. Flotillin-1 and caveolin-1 were markedly decreased concomitantly with a marked increase in gephyrin levels and a less prominent increase in PSD-95. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting that altered LTP post-seizures is a relevant target for antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.pt_PT
dc.description.sponsorshipThis work was supported by the national and international funding managed by the Fundação para a Ciência e a Tecnologia (FCT, IP), Portugal. Grants: FCT UIDB/04046/2020 and UIDP/04046/2020 to BioISI, PTDC/SAU-NEU/103639/2008; and FCT/POCTI (PTDC/SAU-PUB/28311/2017) EPIRaft grant to DC-R. Fellowships: SFRH/BPD/81358/2011 to DC-R and Researcher contract: Norma Transitória–DL57/2016/CP1479/CT0044 to DC-R.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Cell Neurosci . 2023 May 9;17:1117697pt_PT
dc.identifier.doi10.3389/fncel.2023.1117697pt_PT
dc.identifier.eissn1662-5102
dc.identifier.urihttp://hdl.handle.net/10451/57692
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationDL57/2016/CP1479/CT0044pt_PT
dc.relationBiosystems and Integrative Sciences Institute
dc.relationBiosystems and Integrative Sciences Institute
dc.relationContribution of neuronal membrane and lipid raft remodelling to the pathophysiology of mesial temporal lobe epilepsy (MTLE): insight into the beneficial effects of the ketogenic diet therapy.
dc.relationEVALUATING THERAPEUTIC OPPORTUNITIES FOR PREVENTING EPILEPTOGENESIS, COGNITIVE DECLINE AND SUDDEN DEATH IN EPILEPSY
dc.relation.publisherversionhttps://www.frontiersin.org/journals/cellular-neurosciencept_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBicucullinept_PT
dc.subjectEpileptiform activitypt_PT
dc.subjectLipid raftspt_PT
dc.subjectLong term potentiation (LTP)pt_PT
dc.subjectLow Mg2+pt_PT
dc.subjectMesial temporal lobe epilepsy (MTLE)pt_PT
dc.subjectSeizurespt_PT
dc.titleEpileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleContribution of neuronal membrane and lipid raft remodelling to the pathophysiology of mesial temporal lobe epilepsy (MTLE): insight into the beneficial effects of the ketogenic diet therapy.
oaire.awardTitleEVALUATING THERAPEUTIC OPPORTUNITIES FOR PREVENTING EPILEPTOGENESIS, COGNITIVE DECLINE AND SUDDEN DEATH IN EPILEPSY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-NEU%2F103639%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FSAU-PUB%2F28311%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F81358%2F2011/PT
oaire.citation.titleFrontiers in Cellular Neurosciencept_PT
oaire.citation.volume17pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamOE
person.familyNameCruz
person.familyNameHenriques Vaz
person.familyNameJerónimo da Cunha Reis
person.givenNameArmando
person.givenNameSandra Cristina
person.givenNameDiana Lina
person.identifierF-1689-2011
person.identifier.ciencia-id0E1C-952D-61BE
person.identifier.ciencia-id1F1E-73C0-FD44
person.identifier.orcid0000-0002-4403-622X
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0002-0900-9306
person.identifier.scopus-author-id8571270200
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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