Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3 beta inhibition-independent pathways

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dc.authorid0000-0002-6242-3709
dc.contributor.authorDoeppner, Thorsten Roland
dc.contributor.authorKaltwasser, Britta
dc.contributor.authorSanchez-Mendoza, Eduardo H.
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBaehr, Mathias
dc.contributor.authorHermann, Dirk M.
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:57:34Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:57:34Z
dc.date.issued2017
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.descriptionWOS: 000394660400015
dc.descriptionPubMed ID: 27126323
dc.description.abstractLithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3 inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1mg/kg bolus followed by 2mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9h after reperfusion onset. Delivery of lithium no later than 6h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen-glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3 inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis.
dc.description.sponsorshipGerman Research Council ( DFG) [HE3173/2-2, HE3173/3-1]; TUBITAK [2221]en_US
dc.description.sponsorshipThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The present study was supported by the German Research Council (DFG; # HE3173/2-2 and # HE3173/3-1 to DMH) and TUBITAK (# 2221 to TRD).en_US
dc.identifier.citationDoeppner, T. R., Kaltwasser, B., Sanchez-Mendoza, E. H., Çağlayan, A. B., Baehr, M. ve Hermann, D. M. (2017). Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3 beta inhibition-independent pathways. Journal of Cerebral Blood Flow and Metabolism, 37(3), 914-926. https://dx.doi.org/10.1177/0271678X16647738
dc.identifier.doi10.1177/0271678X16647738
dc.identifier.endpage926
dc.identifier.issn0271-678X
dc.identifier.issn1559-7016
dc.identifier.issue3
dc.identifier.scopusqualityQ1
dc.identifier.startpage914
dc.identifier.urihttps://dx.doi.org/10.1177/0271678X16647738
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3006
dc.identifier.volume37
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSage Publication Inc.
dc.relation.ispartofJournal of Cerebral Blood Flow and Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCerebral Ischemia
dc.subjectNeuroregeneration
dc.subjectLithium
dc.subjectmiRNA
dc.subjectStroke
dc.subjectRE1-Silencing Transcription Factor
dc.titleLithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3 beta inhibition-independent pathways
dc.typeArticle

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