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dc.contributor.authorDonoso, Francisco
dc.contributor.authorRamírez, Valerie T
dc.contributor.authorGolubeva, Anna V
dc.contributor.authorMoloney, Gerard M
dc.contributor.authorStanton, Catherine
dc.contributor.authorDinan, Timothy G
dc.contributor.authorCryan, John F
dc.date.accessioned2021-11-23T15:21:02Z
dc.date.available2021-11-23T15:21:02Z
dc.date.issued2019-12-08
dc.identifier.citationDonoso, F., Ramírez, V. T., Golubeva, A. V., Moloney, G. M., Stanton, C., Dinan, T. G., Cryan, J. F., Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons, International Journal of Neuropsychopharmacology, Volume 22, Issue 12, December 2019, Pages 765–777, https://doi.org/10.1093/ijnp/pyz052en_US
dc.identifier.issn1461-1457
dc.identifier.issn1469-5111
dc.identifier.urihttp://hdl.handle.net/11019/2655
dc.descriptionpeer-revieweden_US
dc.description.abstractBackground: Polyphenols are phytochemicals that have been associated with therapeutic effects in stress-related disorders. Indeed, studies suggest that polyphenols exert significant neuroprotection against multiple neuronal injuries, including oxidative stress and neuroinflammation, but the mechanisms are unclear. Evidence indicates that polyphenol neuroprotection may be mediated by activation of Nrf2, a transcription factor associated with antioxidant and cell survival responses. On the other hand, in stress-linked disorders, Fkbp5 is a novel molecular target for treatment because of its capacity to regulate glucocorticoid receptor sensitivity. However, it is not clear the role Fkbp5 plays in polyphenol-mediated stress modulation. In this study, the neuroprotective effects and mechanisms of the naturally derived polyphenols xanthohumol and quercetin against cytotoxicity induced by corticosterone were investigated in primary cortical cells. Methods: Primary cortical cells containing both neurons and astrocytes were pre-incubated with different concentrations of quercetin and xanthohumol to examine the neuroprotective effects of polyphenols on cell viability, morphology, and gene expression following corticosterone insult. Results: Both polyphenols tested prevented the reduction of cell viability and alterations of neuronal/astrocytic numbers due to corticosterone exposure. Basal levels of Bdnf mRNA were also decreased after corticosterone insult; however, this was reversed by both polyphenol treatments. Interestingly, the Nrf2 inhibitor blocked xanthohumol but not quercetin-mediated neuroprotection. In contrast, we found that Fkbp5 expression is exclusively modulated by quercetin. Conclusions: These results suggest that naturally derived polyphenols protect cortical cells against corticosterone-induced cytotoxicity and enhance cell survival via modulation of the Nrf2 pathway and expression of Fkbp5.en_US
dc.language.isoenen_US
dc.publisherOxford University Press (OUP)en_US
dc.relation.ispartofseriesInternational Journal of Neuropsychopharmacology;22
dc.rightsAttribution-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/3.0/us/*
dc.subjectcortical neuronsen_US
dc.subjectcorticosteroneen_US
dc.subjectpolyphenolsen_US
dc.subjectstressen_US
dc.titleNaturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neuronsen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1093/ijnp/pyz052
dc.contributor.sponsorMead Johnsonen_US
dc.contributor.sponsorCremoen_US
dc.contributor.sponsorSuntory Wellnessen_US
dc.contributor.sponsorNutriciaen_US
dc.contributor.sponsor4D Pharmaen_US
dc.contributor.sponsorDuPonten_US
dc.contributor.sponsorScience Foundation Irelanden_US
dc.contributor.sponsorDepartment of Agriculture, Food and the Marineen_US
dc.contributor.sponsorGrantNumberSFI/12/RC/2273en_US
dc.contributor.sponsorGrantNumber13F 411en_US
dc.source.volume22
dc.source.issue12
dc.source.beginpage765-777
refterms.dateFOA2021-11-23T15:21:03Z


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