Differential Effects of Eicosaoentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Neurinal Precursor Cell Proliferation and Neurogenisis

As much as 10% of the US population will experience at least one bout of depression within their lifetime. It has been reported that an increased time spent with major depressive disorder (MDD) results in a decreased volume in the hippocampus. This decreased volume is the result of apoptosis, or programmed cell death. In recent years it has become known that new neurons (neurogenesis) are continuously born in the hippocampus of humans. In fact, it now appears that antidepressant drug efficacy may be dependent on adult neurogenesis in the hippocampus. At least six epidemiological studies have shown an inverse correlation between seafood intake and prevalence of mood disorders (p [less than]0.05 or better). There is mounting evidence that this result is due to fish oils containing the long-chain, poly-unsaturated, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although extensive study has been undertaken using both of these omega-3s together, very little has been done to determine which fatty acid has the greater effect. Although previously thought to be readily interconvertible, there is mounting evidence that these two lipids are not treated equally in the body. EPA has produced greater cell proliferation over DHA in the B-lymphocyte cells, and DHA has even been known to cause a decrease at higher concentrations. Differences have also been reported in both molecular and behavioral outcomes. This research tested the hypothesis that EPA facilitates proliferation and survival of neuronal precursor cells to a greater extent than does DHA. Human neuronal precursor cells were grown in the presence of EPA, DHA, and varying ratios of EPA and DHA to determine their dose-response relationships. While there were no large effects on proliferation or differentiation, EPA, but not DHA, protected cells from iron-induced oxidative stress. This protection appears to be, at least in part, the result of altered p53 translocation in EPA-treated cells. Future work will be needed to determine the role of this molecular protection in the antidepressant activity of EPA.