Phosphodiesterase 10A deactivation induces long-term neurological recovery, peri-infarct remodeling and pyramidal tract plasticity after transient focal cerebral ischemia in mice

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dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-2657-3515
dc.authorid0000-0002-0323-6153
dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-1222-9211
dc.authorid0000-0001-6494-8923
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorPençe, Mahmud Esad
dc.contributor.authorYağmur, Sümeyya
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorÇağlayan, Aysun
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorYelkenci, Hayriye Ecem
dc.contributor.authorAltıntaş, Mehmet Özgen
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorDoeppner, Thorsten Roland
dc.contributor.authorHermann, Dirk M.
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2022-09-27T08:08:05Z
dc.date.available2022-09-27T08:08:05Z
dc.date.issued2022
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Genetik Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractThe phosphodiesterase (PDE) superfamily comprises enzymes responsible for the cAMP and cGMP degradation to AMP and GMP. PDEs are abundant in the brain, where they are involved in several neuronal functions. High PDE10A abundance was previously observed in the striatum; however its consequences for stroke recovery were unknown. Herein, we evaluated the effects of PDE10A deactivation by TAK-063 (0.3 or 3 mg/kg, initiated 72 h post-stroke) in mice exposed to intraluminal middle cerebral artery occlusion. We found that PDE10A deactivation over up to eight weeks dose-dependently increased long-term neuronal survival, angiogenesis, and neurogenesis in the peri-infarct striatum, which represents the core of the middle cerebral artery territory, and reduced astroglial scar formation, whole brain atrophy and, more specifically, striatal atrophy. Functional motor-coordination recovery and the long-distance plasticity of pyramidal tract axons, which originate from the contralesional motor cortex and descend through the contralesional striatum to innervate the ipsilesional facial nucleus, were enhanced by PDE10A deactivation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed a set of dopamine receptor-related and neuronal plasticity-related PDE10A targets, which were elevated (e.g., protein phosphatase-1 regulatory subunit 1B) or reduced (e.g., serine/threonine protein phosphatase 1?, ?-synuclein, proteasome subunit ?2) by PDE10A deactivation. Our results identify PDE10A as a therapeutic target that critically controls post-ischemic brain tissue remodeling and plasticity.
dc.identifier.citationBeker, M. Ç., Pençe, M. E., Yağmur, S., Çağlayan, B., Çağlayan, A., Kılıç, Ü. ... Kılıç, E. (2022). Phosphodiesterase 10A deactivation induces long-term neurological recovery, peri-infarct remodeling and pyramidal tract plasticity after transient focal cerebral ischemia in mice. Experimental Neurology, 358. https://dx.doi.org/10.1016/j.expneurol.2022.114221
dc.identifier.doi10.1016/j.expneurol.2022.114221
dc.identifier.issn0014-4886
dc.identifier.pmid36075453
dc.identifier.scopus2-s2.0-85137279937
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.1016/j.expneurol.2022.114221
dc.identifier.urihttps://hdl.handle.net/20.500.12511/9755
dc.identifier.volume358
dc.identifier.wos000932091100006en_US
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorBeker, Mustafa Çağlar
dc.institutionauthorPençe, Mahmud Esad
dc.institutionauthorYağmur, Sümeyya
dc.institutionauthorÇağlayan, Berrak
dc.institutionauthorÇağlayan, Aysun
dc.institutionauthorYelkenci, Hayriye Ecem
dc.institutionauthorAltıntaş, Mehmet Özgen
dc.institutionauthorÇağlayan, Ahmet Burak
dc.institutionauthorDoeppner, Thorsten Roland
dc.institutionauthorKılıç, Ertuğrul
dc.language.isoen
dc.publisherAcademic Press Inc.
dc.relation.ispartofExperimental Neurologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAnterograde Tract-Tracing
dc.subjectAxonal Plasticity
dc.subjectcAMP
dc.subjectcGMP
dc.subjectDelayed Neuronal Degeneration
dc.subjectFocal Cerebral Ischemia
dc.titlePhosphodiesterase 10A deactivation induces long-term neurological recovery, peri-infarct remodeling and pyramidal tract plasticity after transient focal cerebral ischemia in mice
dc.typeArticle

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