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Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons
BACKGROUND: 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 mechanis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929673/ https://www.ncbi.nlm.nih.gov/pubmed/31812985 http://dx.doi.org/10.1093/ijnp/pyz052 |
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author | Donoso, Francisco Ramírez, Valerie T Golubeva, Anna V Moloney, Gerard M Stanton, Catherine Dinan, Timothy G Cryan, John F |
author_facet | Donoso, Francisco Ramírez, Valerie T Golubeva, Anna V Moloney, Gerard M Stanton, Catherine Dinan, Timothy G Cryan, John F |
author_sort | Donoso, Francisco |
collection | PubMed |
description | BACKGROUND: 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. |
format | Online Article Text |
id | pubmed-6929673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-69296732019-12-30 Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons Donoso, Francisco Ramírez, Valerie T Golubeva, Anna V Moloney, Gerard M Stanton, Catherine Dinan, Timothy G Cryan, John F Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: 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. Oxford University Press 2019-12-08 /pmc/articles/PMC6929673/ /pubmed/31812985 http://dx.doi.org/10.1093/ijnp/pyz052 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium,provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Regular Research Articles Donoso, Francisco Ramírez, Valerie T Golubeva, Anna V Moloney, Gerard M Stanton, Catherine Dinan, Timothy G Cryan, John F Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title | Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title_full | Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title_fullStr | Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title_full_unstemmed | Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title_short | Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons |
title_sort | naturally derived polyphenols protect against corticosterone-induced changes in primary cortical neurons |
topic | Regular Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929673/ https://www.ncbi.nlm.nih.gov/pubmed/31812985 http://dx.doi.org/10.1093/ijnp/pyz052 |
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