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

Chronic exposure to the glucocorticoid hormone corticosterone (CORT) exerts cellular stress-induced toxic effects which have been associated with neurodegenerative and psychiatric disorders. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid that has been shown to be of benefit in stress related disorders, putatively through protective action in neurons. We investigated the protective effect of DHA against CORT-induced cellular changes in cortical cell cultures containing both astrocytes and neurons. We found that CORT (100, 150, 200 uM) at different time points (48, 72 hours), induced a dose- and time-dependent reduction in cellular viability as assessed by methyl thiazolyl tetrazolium (MTT). Moreover, CORT (200 uM - 72 hours) decreased the percentage composition of neurons whilst increasing the percentage of astrocytes as assessed by âIII-tubulin and GFAP immunostaining, respectively. In contrast, DHA treatment (6 uM) increased DHA content and attenuated CORT (200 uM)-induced cell death (72 hours) in cortical cultures. This translates into a capacity for DHA to prevent neuronal death as well as astrocyte overgrowth following chronic exposure to CORT. Furthermore, DHA (6 uM) reversed CORT-induced neuronal apoptosis as assessed by TUNEL, and attenuated CORT-induced reductions in BDNF mRNA expression in these cultures. Finally, DHA inhibited CORT-induced down-regulation of GR expression on âIII- tubulin-positive neurons. This work supports the view that DHA may be beneficial in ameliorating stress-related cellular changes in the brain and may be of value in psychiatric disorders.