Pusceddu MM, Nolan YM, Green HF, Robertson RC, Stanton C, Kelly P, Cryan JF, Dinan TG. (2015) Int J Neuropsychopharmacol. 2015 Dec 12. pii: pyv130. doi: 10.1093/ijnp/pyv130. [Epub ahead of print]
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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.
© The Author 2015. Published by Oxford University Press on behalf of CINP.