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dc.contributor.authorAkin, Demet
dc.contributor.authorRavizza, Teresa
dc.contributor.authorMaroso, Mattia
dc.contributor.authorCarcak, Nihan
dc.contributor.authorEryigit, Tugba
dc.contributor.authorVanzulli, Ilaria
dc.contributor.authorOnat, Filiz Yilmaz
dc.date.accessioned2019-08-13T12:10:23Z
dc.date.accessioned2019-08-13T16:03:56Z
dc.date.available2019-08-13T12:10:23Z
dc.date.available2019-08-13T16:03:56Z
dc.date.issued2011
dc.identifier.issn0969-9961
dc.identifier.issn1095-953X
dc.identifier.urihttps://dx.doi.org/10.1016/j.nbd.2011.05.015
dc.identifier.urihttp://hdl.handle.net/11446/3197
dc.descriptionWOS: 000295816200001en_US
dc.descriptionPubMed ID: 21645619en_US
dc.description.abstractInterleukin (IL)-1 beta plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1 beta signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1 beta biosynthesis in GAERS could affect SWD activity. IL-1 beta expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet. UT immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1 beta was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1 beta was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1 beta biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1 beta is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1 beta has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures. (C) 2011 Elsevier Inc. All rights reserved.en_US
dc.description.sponsorshipMarmara University Scientific Research Committee [SAG-075/120503]; Istanbul Bilim University Scientific Research Committee; EPICURE [LSH-CT-2006-037315]; Fondazione Monzino; NeuroGlia [202167]en_US
dc.description.sponsorshipThis study was supported by the Marmara University Scientific Research Committee (SAG-075/120503, F.Y.O.), Istanbul Bilim University Scientific Research Committee (D. A.), EPICURE (LSH-CT-2006-037315, A. V.) and Fondazione Monzino (A.V.). Mattia Maroso received a fellowship from NeuroGlia (EU-FP7-project 202167). The authors are grateful to Vertex Pharmaceuticals Incorporated for supplying VX-765 and to Irina Kadiyala (Vertex Pharmaceuticals Incorporated) for her support with the drug formulation.en_US
dc.language.isoengen_US
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEen_US
dc.identifier.doi10.1016/j.nbd.2011.05.015en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectInflammationen_US
dc.subjectAbsence seizuresen_US
dc.subjectInterleukinsen_US
dc.subjectSWDen_US
dc.titleIL-1 beta is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrenceen_US
dc.typearticleen_US
dc.relation.journalNEUROBIOLOGY OF DISEASEen_US
dc.departmentDBÜen_US
dc.identifier.issue3en_US
dc.identifier.volume44en_US
dc.identifier.startpage259en_US
dc.identifier.endpage269en_US
dc.contributor.authorID0000-0003-0680-4782en_US
dc.contributor.authorID0000-0002-1519-3170en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.department-temp[Ravizza, Teresa -- Maroso, Mattia -- Vanzulli, Ilaria -- Vezzani, Annamaria] Mario Negri Inst Pharmacol Res, Dept Neurosci, I-20156 Milan, Italy -- [Akin, Demet] Istanbul Bilim Univ, Dept Pharmacol, Sch Med, Istanbul, Turkey -- [Carcak, Nihan] Istanbul Univ, Fac Pharm, Dept Pharmacol, Istanbul, Turkey -- [Eryigit, Tugba -- Aker, Rezzan Gulhan -- Onat, Filiz Yilmaz] Marmara Univ, Dept Pharmacol & Clin Pharmacol, Sch Med, Istanbul, Turkeyen_US


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