Involvement of Akt/CREB signaling pathways in the protective effect of EPA against interleukin-1β-induced cytotoxicity and BDNF down-regulation in cultured rat hippocampal neurons

Background: Our published data have indicated that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating neuronal damage induced by interleukin-1 beta(IL-1 beta), and up-regulation of the expression of brain-derived neurotrophic factor (BDNF) represents a crucial part in the neuroprotective effect of EPA. However, the mechanisms of how EPA regulates BDNF expression remains incompletely understood. The present study investigated the role of Akt/CREB signaling in the effect of EPA on BDNF expression and its neuroprotective effect. Results: The present results showed that IL-1 beta reduced hippocampal neuronal viability and that EPA showed a concentration-dependent neuroprotective effect, but the neuroprotective effects of EPA were abolished by inhibition of Akt using KRX-0401, an inhibitor of Akt. Treatment of hippocampal neurons with EPA also ameliorated the decrease in Akt and CREB phosphorylation induced by IL-1 beta and BDNF down-regulation mediated by IL-1 beta. However, inhibition of Akt reversed the effect of EPA on levels of p-Akt, p-CREB, and BDNF. Conclusions: Our data indicate that EPA elicited neuroprotection toward IL-1 beta-induced cell damage and BDNF decrease and that its effects potentially occurred via the Akt/CREB signaling pathway.