Evidence that activation of P2X7R does not exacerbate neuronal death after optic nerve transection and focal cerebral ischemia in mice

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dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-1064-7989
dc.authorid0000-0003-3616-1204
dc.authorid0000-0003-0352-1947
dc.authorid0000-0002-6895-8560
dc.authorid0000-0001-6494-8923
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorYalçın, Esra
dc.contributor.authorBeker, Merve
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorSertel, Elif
dc.contributor.authorÖztürk, Gürkan
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorŞahin, Fikrettin
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:55:59Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:55:59Z
dc.date.issued2017
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.descriptionWOS: 000408296600003
dc.descriptionPubMed ID: 28669743
dc.description.abstractConflicting data in the literature about the function of P2X7R in survival following ischemia necessitates the conductance of in-depth studies. To investigate the impacts of activation vs inhibition of the receptor on neuronal survival as well as the downstream signaling cascades, in addition to optic nerve transection (ONT), 30 min and 90 min of middle cerebral artery occlusion (MCAo) models were performed in mice. Intracellular calcium levels were assessed in primary cortical neuron cultures. Here, we show that P2X7R antagonist Brilliant Blue G (BBG) decreased DNA fragmentation, infarct volume, brain swelling, neurological deficit scores and activation of microglial cells after focal cerebral ischemia. BBG also significantly increased the number of surviving retinal ganglion cells (RGCs) after ONT and the number of surviving neurons following MCAo. Importantly, receptor agonist BzATP resulted in increased activation of microglial cells and induced phosphorylation of ERK,AKT and JNK. These results indicated that inhibition of P2X7R with BBG promoted neuronal survival, not through the activation of survival kinase pathways, but possibly by improved intracellular Ca2+ overload and decreased the levels of Caspase 1, IL-1 beta and Bax proteins. On the other hand, BzATP-mediated increased number of activated microglia and increased survival kinase levels in addition to increased caspase-1 and IL-1 beta levels indicate the complex nature of the P2X7 receptor-mediated signaling in neuronal injury.
dc.description.sponsorshipTurkish Academy of Sciences (TUBA)en_US
dc.description.sponsorshipThis work was supported by Turkish Academy of Sciences (TUBA).en_US
dc.identifier.citationÇağlayan, B., Çağlayan, A. B., Beker, M. Ç., Yalçın, E., Beker, M., Keleştemur, T. … Kılıç, E. (2017). Evidence that activation of P2X7R does not exacerbate neuronal death after optic nerve transection and focal cerebral ischemia in mice. Experimental Neurology, 296, 23-31. https://dx.doi.org/10.1016/j.expneurol.2017.06.024
dc.identifier.doi10.1016/j.expneurol.2017.06.024
dc.identifier.endpage31
dc.identifier.issn0014-4886
dc.identifier.issn1090-2430
dc.identifier.scopusqualityQ1
dc.identifier.startpage23
dc.identifier.urihttps://dx.doi.org/10.1016/j.expneurol.2017.06.024
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2510
dc.identifier.volume296
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofExperimental Neurologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectP2X7 Receptor
dc.subjectNeuronal Survival
dc.subjectSignaling
dc.subjectCerebral Ischemia
dc.subjectOptic Nerve Transection
dc.titleEvidence that activation of P2X7R does not exacerbate neuronal death after optic nerve transection and focal cerebral ischemia in mice
dc.typeArticle

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