The Omega-3 Polyunsaturated Fatty acid Docosahexaenoic acid (DHA) reverses Corticosterone-induced Changes in Cortical neurons

Abstract:

BACKGROUND:

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.

METHODS:

We investigated the protective effect of DHA against CORT-induced cellular changes in cortical cell cultures containing both astrocytes and neurons.

RESULTS:

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.

CONCLUSIONS:

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.