The Role of Glycogen Synthase Kinase-3? in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicity

Basit Öğe Kaydı
dc.authoridORUÇ, Kadriye Yağmur/0000-0002-3747-5136
dc.authoridOZTURK KURT, B/0000-0002-1171-002X
dc.authoridORUC, Aykut/0000-0001-8043-7971;
dc.authorwosidCakatay, Ufuk/D-2752-2015
dc.authorwosidUzun, Hafize/D-4811-2019
dc.authorwosidORUÇ, Kadriye Yağmur/AAR-9552-2020
dc.authorwosidOZTURK KURT, B/AGR-3268-2022
dc.authorwosidÇağlar, AYSEL/V-6518-2017
dc.authorwosidÇağlar, Aysel/GPG-3623-2022
dc.authorwosidORUC, Aykut/HSI-3255-2023
dc.contributor.authorOruc, Aykut
dc.contributor.authorOruc, Kadriye Yagmur
dc.contributor.authorYanar, Karolin
dc.contributor.authorMengi, Murat
dc.contributor.authorCaglar, Aysel
dc.contributor.authorKurt, Bahar Ozturk
dc.contributor.authorAltan, Mehmet
dc.date.accessioned2024-05-19T14:41:54Z
dc.date.available2024-05-19T14:41:54Z
dc.date.issued2024
dc.departmentİstinye Üniversitesien_US
dc.description.abstractMetformin has been suggested to have protective effects on the central nervous system, but the mechanism is unknown. The similarity between the effects of metformin and the inhibition of glycogen synthase kinase (GSK)-3 beta suggests that metformin may inhibit GSK-3 beta. In addition, zinc is an important element that inhibits GSK-3 beta by phosphorylation. In this study, we investigated whether the effects of metformin on neuroprotection and neuronal survival were mediated by zinc-dependent inhibition of GSK-3 beta in rats with glutamate-induced neurotoxicity. Forty adult male rats were divided into 5 groups: control, glutamate, metformin + glutamate, zinc deficiency + glutamate, and zinc deficiency + metformin + glutamate. Zinc deficiency was induced with a zinc-poor pellet. Metformin was orally administered for 35 days. D-glutamic acid was intraperitoneally administered on the 35th day. On the 38th day, neurodegeneration was examined histopathologically, and the effects on neuronal protection and survival were evaluated via intracellular S-100 beta immunohistochemical staining. The findings were examined in relation to nonphosphorylated (active) GSK-3 beta levels and oxidative stress parameters in brain tissue and blood. Neurodegeneration was increased (p < 0.05) in rats fed a zinc-deficient diet. Active GSK-3 beta levels were increased in groups with neurodegeneration (p < 0.01). Decreased neurodegeneration, increased neuronal survival (p < 0.01), decreased active GSK-3 beta ( p < 0.01) levels and oxidative stress parameters, and increased antioxidant parameters were observed in groups treated with metformin (p < 0.01). Metformin had fewer protective effects on rats fed a zinc-deficient diet. Metformin may exert neuroprotective effects and increase S-100 beta-mediated neuronal survival by zinc-dependent inhibition of GSK-3 beta during glutamate neurotoxicity.en_US
dc.description.sponsorshipIstanbul University Scientific Research Projects [27509]en_US
dc.description.sponsorshipThis study was funded by the Istanbul University Scientific Research Projects. Project No: 27509.en_US
dc.identifier.doi10.1007/s12011-023-03667-3
dc.identifier.endpage245en_US
dc.identifier.issn0163-4984
dc.identifier.issn1559-0720
dc.identifier.issue1en_US
dc.identifier.pmid37071257en_US
dc.identifier.scopus2-s2.0-85153106058en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage233en_US
dc.identifier.urihttps://doi.org10.1007/s12011-023-03667-3
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5175
dc.identifier.volume202en_US
dc.identifier.wosWOS:000974538400001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringernatureen_US
dc.relation.ispartofBiological Trace Element Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240519_kaen_US
dc.subjectGlutamateen_US
dc.subjectGsk-3 Betaen_US
dc.subjectMetforminen_US
dc.subjectNeurotoxicityen_US
dc.subjectS-100 Betaen_US
dc.subjectZincen_US
dc.titleThe Role of Glycogen Synthase Kinase-3? in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicityen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
Temel Tıp Bilimleri Bölümü Diğer Yayınlar Koleksiyonu