The Omega-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid (DHA) Reverses Corticosterone-Induced Changes in Cortical Neurons

Matteo M Pusceddu; Yvonne M Nolan; Holly F Green; Ruairi C Robertson; Catherine Stanton; Philip Kelly; John F Cryan; Timothy G Dinan

doi:10.1093/ijnp/pyv130

The Omega-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid (DHA) Reverses Corticosterone-Induced Changes in Cortical Neurons

Int J Neuropsychopharmacol. 2016 Jun 1;19(6):pyv130. doi: 10.1093/ijnp/pyv130. Epub 2015 Dec 12.

Authors

Matteo M Pusceddu¹, Yvonne M Nolan¹, Holly F Green¹, Ruairi C Robertson¹, Catherine Stanton¹, Philip Kelly¹, John F Cryan², Timothy G Dinan¹

Affiliations

¹ Department of Psychiatry and Neurobehavioural Science (Dr Pusceddu and Prof. Dinan), APC Microbiome Institute (Drs Pusceddu and Stanton and Profs Cryan and Dinan), Department of Anatomy and Neuroscience (Drs Nolan and Green and Prof. Cryan), and School of Microbiology, University College Cork, Cork, Ireland (Mr Robertson); Moorepark Food Research Centre, Teagasc, Fermoy, Co. Cork, Ireland (Mr Robertson and Drs Stanton and Kelly).
² Department of Psychiatry and Neurobehavioural Science (Dr Pusceddu and Prof. Dinan), APC Microbiome Institute (Drs Pusceddu and Stanton and Profs Cryan and Dinan), Department of Anatomy and Neuroscience (Drs Nolan and Green and Prof. Cryan), and School of Microbiology, University College Cork, Cork, Ireland (Mr Robertson); Moorepark Food Research Centre, Teagasc, Fermoy, Co. Cork, Ireland (Mr Robertson and Drs Stanton and Kelly). j.cryan@ucc.ie.

Abstract

Background: 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.

Keywords: Docosahexaenoic acid; brain derived neurotrophic factor; corticosterone; glucocorticoid receptors; stress.