The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) reverses corticosterone-induced changes in cortical neurons

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dc.contributor.authorPusceddu, Matteo M.
dc.contributor.authorNolan, Yvonne M.
dc.contributor.authorGreen, Holly F.
dc.contributor.authorRobertson, Ruairi C.
dc.contributor.authorStanton, Catherine
dc.contributor.authorKelly, Philip M.
dc.contributor.authorCryan, John F.
dc.contributor.authorDinan, Timothy G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderDepartment of Agriculture, Food and the Marineen
dc.date.accessioned2017-03-08T15:14:09Z
dc.date.available2017-03-08T15:14:09Z
dc.date.issued2015-12-12
dc.date.updated2017-03-08T14:36:34Z
dc.description.abstractBackground: Chronic exposure to the glucocorticoid hormone corticosterone exerts cellular stress-induced toxic effects that have been associated with neurodegenerative and psychiatric disorders. Docosahexaenoic acid is a polyunsaturated fatty acid that has been shown to be of benefit in stress-related disorders, putatively through protective action in neurons. Methods: We investigated the protective effect of docosahexaenoic acid against glucocorticoid hormone corticosterone-induced cellular changes in cortical cell cultures containing both astrocytes and neurons. Results: We found that glucocorticoid hormone corticosterone (100, 150, 200 μM) at different time points (48 and 72 hours) induced a dose- and time-dependent reduction in cellular viability as assessed by methyl thiazolyl tetrazolium. Moreover, glucocorticoid hormone corticosterone (200 μM, 72 hours) decreased the percentage composition of neurons while increasing the percentage of astrocytes as assessed by βIII-tubulin and glial fibrillary acidic protein immunostaining, respectively. In contrast, docosahexaenoic acid treatment (6 μM) increased docosahexaenoic acid content and attenuated glucocorticoid hormone corticosterone (200 μM)-induced cell death (72 hours) in cortical cultures. This translates into a capacity for docosahexaenoic acid to prevent neuronal death as well as astrocyte overgrowth following chronic exposure to glucocorticoid hormone corticosterone. Furthermore, docosahexaenoic acid (6 μM) reversed glucocorticoid hormone corticosterone-induced neuronal apoptosis as assessed by terminal deoxynucleotidyl transferase–mediated nick-end labeling and attenuated glucocorticoid hormone corticosterone-induced reductions in brain derived neurotrophic factor mRNA expression in these cultures. Finally, docosahexaenoic acid inhibited glucocorticoid hormone corticosterone-induced downregulation of glucocorticoid receptor expression on βIII- tubulin-positive neurons. Conclusions: This work supports the view that docosahexaenoic acid may be beneficial in ameliorating stress-related cellular changes in the brain and may be of value in psychiatric disorders.en
dc.description.sponsorshipDepartment of Agriculture, Food and the Marine (Food Institutional Research Measure, FIRM (grant number 10/RD/TMFRC/709)); Science Foundation Ireland (centre grant (Alimentary Pharmabiotic Centre grant no. SFI/12/RC/2273), Investigator Award (grant no. 12/IA/1537))en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPusceddu, M. M., Nolan, Y. M., Green, H. F., Robertson, R. C., Stanton, C., Kelly, P., Cryan, J. F. and Dinan, T. G. (2016) 'The Omega-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid (DHA) Reverses Corticosterone-Induced Changes in Cortical Neurons', International Journal of Neuropsychopharmacology, 19(6), pyv130. doi:10.1093/ijnp/pyv130en
dc.identifier.doi10.1093/ijnp/pyv130
dc.identifier.endpagepyv130-10en
dc.identifier.issn1469-5111
dc.identifier.issued6en
dc.identifier.journaltitleInternational Journal of Neuropsychopharmacologyen
dc.identifier.startpagepyv130-1en
dc.identifier.urihttps://hdl.handle.net/10468/3759
dc.identifier.volume9en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rights© The Authors 2015. Published by Oxford University Press on behalf of CINP. 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.comen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectDocosahexaenoic aciden
dc.subjectCorticosteroneen
dc.subjectStressen
dc.subjectGlucocorticoid receptorsen
dc.subjectBrain derived neurotrophic factoren
dc.titleThe omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) reverses corticosterone-induced changes in cortical neuronsen
dc.typeArticle (peer-reviewed)en
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