Naturally derived polyphenols protect against corticosterone-induced changes in primary cortical neurons

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dc.contributor.authorDonoso, Francisco
dc.contributor.authorRamirez, 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.contributor.funderScience Foundation Irelanden
dc.contributor.funderDepartment of Agriculture, Food and the Marine, Irelanden
dc.contributor.funderMead Johnson Nutritionen
dc.contributor.funderCremoen
dc.contributor.funderSuntory Wellnessen
dc.contributor.funderNutriciaen
dc.contributor.funder4D Pharmaen
dc.contributor.funderDuPonten
dc.date.accessioned2022-04-06T09:48:03Z
dc.date.available2022-04-06T09:48:03Z
dc.date.issued2019-12
dc.date.updated2022-04-06T09:12:50Z
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
dc.description.sponsorshipDepartment of Agriculture, Food and the Marine, Ireland (Grant no. 13F 411)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDonoso, F., Ramirez, V. T., Golubeva, A. V., Moloney, G. M., Stanton, C., Dinan, T. G. and Cryan, J. F. (2019) 'Naturally derived polyphenols protect against corticosterone-induced changes in primary cortical neurons', International Journal of Neuropsychopharmacology, 22 (12) pp. 765-777. doi: 10.1093/ijnp/pyz052en
dc.identifier.doi10.1093/ijnp/pyz052en
dc.identifier.endpage777en
dc.identifier.issn1461-1457
dc.identifier.issued12en
dc.identifier.journaltitleInternational Journal of Neuropsychopharmacologyen
dc.identifier.startpage765en
dc.identifier.urihttps://hdl.handle.net/10468/13036
dc.identifier.volume22en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectGlucocorticoid-receptoren
dc.subjectInduced apoptosisen
dc.subjectNeurotrophic factoren
dc.subjectPrefrontal cortexen
dc.subjectMajor depressionen
dc.subjectCell-deathen
dc.subjectHpa-axisen
dc.subjectTranscription factoren
dc.subjectGene-expressionen
dc.subjectChronic stressen
dc.titleNaturally derived polyphenols protect against corticosterone-induced changes in primary cortical neuronsen
dc.typeArticle (peer-reviewed)en
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