Delayed therapeutic administration of melatonin enhances neuronal survival through AKT and MAPK signaling pathways following focal brain ischemia in mice

dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-9476-8488
dc.authorid0000-0001-6494-8923
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorElibol, Birsen
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorBeker, Merve
dc.contributor.authorAltuğ Tasa, ?Burcugül
dc.contributor.authorUysal, Ömer
dc.contributor.authorYılmaz, Bayram
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned2022-11-18T12:43:03Z
dc.date.available2022-11-18T12:43:03Z
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.description.abstractMelatonin has a role in the cell survival signaling pathways as a candidate for secondary stroke prevention. Therefore, in the present study, the coordination of ipsilateral and contralateral hemispheres to evaluate delayed post-acute effect of melatonin was examined on recovery of the cell survival and apoptosis after stroke. Melatonin was administered (4 mg/kg/day) intraperitoneally for 45 days, starting 3 days after 30 min of middle cerebral artery occlusion. The genes and proteins related to the cell survival and apoptosis were investigated by immunofluorescence, western blotting, and RT-PCR techniques after behavioral experiments. Melatonin produced delayed neurological recovery by improving motor coordination on grip strength and rotarod tests. This neurological recovery was also reflected by high level of NeuN positive cells and low level of TUNEL-positive cells suggesting enhanced neuronal survival and reduced apoptosis at the fifty-fifth day of stroke. The increase of NGF, Nrp1, c-jun; activation of AKT; and dephosphorylation of ERK and INK at the fifty-fifth day showed that cell survival and apoptosis signaling molecules compete to contribute to the remodeling of brain. Furthermore, an increase in the CREB and Atf-1 expressions suggested the melatonin's strong reformative effect on neuronal regeneration. The contralateral hemisphere was more active at the latter stages of the molecular and functional regeneration which provides a further proof of principle about melatonin's action on the promotion of brain plasticity and recovery after stroke.
dc.identifier.citationKılıç, Ü., Elibol, B., Çağlayan, A. B., Beker, M. Ç., Beker, M., Altuğ Tasa, ?B. ... Kılıç, E. (2022). Delayed therapeutic administration of melatonin enhances neuronal survival through AKT and MAPK signaling pathways following focal brain ischemia in mice. Journal of Molecular Neuroscience, 72(5), 994-1007. https://doi.org/10.1007/s12031-022-01995-y
dc.identifier.doi10.1007/s12031-022-01995-y
dc.identifier.endpage1007
dc.identifier.issn0895-8696
dc.identifier.issn1559-1166
dc.identifier.issue5
dc.identifier.pmid35307786
dc.identifier.scopus2-s2.0-85126790431
dc.identifier.scopusqualityQ2
dc.identifier.startpage994
dc.identifier.urihttps://doi.org/10.1007/s12031-022-01995-y
dc.identifier.urihttps://hdl.handle.net/20.500.12511/9993
dc.identifier.volume72
dc.identifier.wos000770956000001en_US
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorÇağlayan, Ahmet Burak
dc.institutionauthorBeker, Mustafa Çağlar
dc.institutionauthorKılıç, Ertuğrul
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.ispartofJournal of Molecular Neuroscienceen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/111S418
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectApoptosis
dc.subjectBrain Plasticity
dc.subjectCell Survival
dc.subjectIschemic Brain
dc.subjectMelatonin
dc.titleDelayed therapeutic administration of melatonin enhances neuronal survival through AKT and MAPK signaling pathways following focal brain ischemia in mice
dc.typeArticle

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