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dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorAltunay, Serdar
dc.contributor.authorÖzbay, Elif
dc.contributor.authorAteş, Nilay
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorDoeppner, Thorsten Roland
dc.contributor.authorHermann, Dirk Matthias
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2023-01-05T12:15:29Z
dc.date.available2023-01-05T12:15:29Z
dc.date.issued2022en_US
dc.identifier.citationBeker, M. Ç., Çağlayan, A. B., Altunay, S., Özbay, E., Ateş, N., Keleştemur, T. ... Kılıç, E. (2022). Phosphodiesterase 10A is a critical target for neuroprotection in a mouse model of ischemic stroke. Molecular Neurobiology, 59(1), 574-589. https://dx.doi.org/10.1007/s12035-021-02621-5en_US
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.urihttps://dx.doi.org/10.1007/s12035-021-02621-5
dc.identifier.urihttps://hdl.handle.net/20.500.12511/10248
dc.description.abstractPhosphodiesterase 10A (PDE10A) hydrolyzes adenosine 3 ',5 '-cyclic monophosphate (cAMP) and guanosine 3 ',5 '-cyclic monophosphate (cGMP). It is highly expressed in the striatum. Recent evidence implied that PDE10A may be involved in the inflammatory processes following injury, such as ischemic stroke. Its role in ischemic injury was unknown. Herein, we exposed mice to 90 or 30-min middle cerebral artery occlusion, followed by the delivery of the highly selective PDE10A inhibitor TAK-063 (0.3 mg/kg or 3 mg/kg) immediately after reperfusion. Animals were sacrificed after 24 or 72 h, respectively. Both TAK-063 doses enhanced neurological function, reduced infarct volume, increased neuronal survival, reduced brain edema, and increased blood-brain barrier integrity, alongside cerebral microcirculation improvements. Post-ischemic neuroprotection was associated with increased phosphorylation (i.e., activation) of pro-survival Akt, Erk-1/2, GSK-3 alpha/beta and anti-apoptotic Bcl-xL abundance, decreased phosphorylation of pro-survival mTOR, and HIF-1 alpha, MMP-9 and pro-apoptotic Bax abundance. Interestingly, PDE10A inhibition reduced inflammatory cytokines/chemokines, including IFN-gamma and TNF-alpha, analyzed by planar surface immunoassay. In addition, liquid chromatography-tandem mass spectrometry revealed 40 proteins were significantly altered by TAK-063. Our study established PDE10A as a target for ischemic stroke therapy.en_US
dc.description.sponsorshipTurkish Academy of Sciencesen_US
dc.language.isoengen_US
dc.publisherSpringeren_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectcAMPen_US
dc.subjectFocal Cerebral Ischemiaen_US
dc.subjectInflammationen_US
dc.subjectPDE10Aen_US
dc.subjectPhosphodiesteraseen_US
dc.subjectTAK-063en_US
dc.titlePhosphodiesterase 10A is a critical target for neuroprotection in a mouse model of ischemic strokeen_US
dc.typearticleen_US
dc.relation.ispartofMolecular Neurobiologyen_US
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)en_US
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsüen_US
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalıen_US
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Genetik Ana Bilim Dalıen_US
dc.authorid0000-0002-9476-8488en_US
dc.authorid0000-0002-6242-3709en_US
dc.authorid0000-0002-4051-2559en_US
dc.authorid0000-0002-6637-9944en_US
dc.authorid0000-0003-3616-1204en_US
dc.authorid0000-0002-5072-132Xen_US
dc.authorid0000-0001-6494-8923en_US
dc.identifier.volume59en_US
dc.identifier.issue1en_US
dc.identifier.startpage574en_US
dc.identifier.endpage589en_US
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/218S453
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1007/s12035-021-02621-5en_US
dc.institutionauthorBeker, Mustafa Çağlar
dc.institutionauthorÇağlayan, Ahmet Burak
dc.institutionauthorAltunay, Serdar
dc.institutionauthorÖzbay, Elif
dc.institutionauthorAteş, Nilay
dc.institutionauthorKeleştemur, Taha
dc.institutionauthorÇağlayan, Berrak
dc.institutionauthorKılıç, Ertuğrul
dc.identifier.wosqualityQ2en_US
dc.identifier.wos000714490000001en_US
dc.identifier.scopus2-s2.0-85118575460en_US
dc.identifier.pmid34735672en_US
dc.identifier.scopusqualityQ1en_US


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