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

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dc.authoridAltan, Mehmet/0000-0002-3275-1234
dc.authoridCakatay, Ufuk/0000-0001-9861-7380
dc.authoridORUC, Aykut/0000-0001-8043-7971
dc.authorid/0000-0002-1171-002X
dc.authoridORUC, Kadriye Yagmur/0000-0002-3747-5136
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.accessioned2024-10-29T17:58:21Z
dc.date.available2024-10-29T17:58:21Z
dc.date.issued2024
dc.departmentTekirdağ Namık Kemal Üniversitesi
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.
dc.description.sponsorshipIstanbul University Scientific Research Projects [27509]
dc.description.sponsorshipThis study was funded by the Istanbul University Scientific Research Projects. Project No: 27509.
dc.identifier.doi10.1007/s12011-023-03667-3
dc.identifier.endpage245
dc.identifier.issn0163-4984
dc.identifier.issn1559-0720
dc.identifier.issue1en_US
dc.identifier.pmid37071257
dc.identifier.scopus2-s2.0-85153106058
dc.identifier.scopusqualityQ1
dc.identifier.startpage233
dc.identifier.urihttps://doi.org/10.1007/s12011-023-03667-3
dc.identifier.urihttps://hdl.handle.net/20.500.11776/14250
dc.identifier.volume202
dc.identifier.wosWOS:000974538400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringernature
dc.relation.ispartofBiological Trace Element Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGlutamate
dc.subjectGSK-3 beta
dc.subjectMetformin
dc.subjectNeurotoxicity
dc.subjectS-100 beta
dc.subjectZinc
dc.titleThe Role of Glycogen Synthase Kinase-3? in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicity
dc.typeArticle

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