Abstract # 3085 Rescue of cytokines induced reduction of human neurogenesis and increase in apoptosis by Omega-3 fatty acids

Abstract

Increased inflammation and reduced neurogenesis are associated with the pathophysiology of depression. We have previously described how distinct pro-inflammatory cytokines involved in depression, including interleukin(IL)-1beta,IL-6 and interferon(IFN)-alpha decrease neurogenesis and increase apoptosis in human hippocampal progenitors. Here, using the same human in vitro model, we show how omega-3 fatty acids prevent the reduction in neurogenesis and increase in apoptosis. We allowed cells to proliferate for 3 days and further differentiate for 7 days in the presence of IL-1beta(10 ng/ml),IL-6(5 pg/ml) and IFN-alpha(5000 pg/ml) alone or in combination with omega-3 eicosapentaenoic acid (EPA,10 μ M) or docosahexaenoic acid (DHA,10 μ M). Immunocytochemistry was performed to identify neuronal differentiation (microtubule associated protein-2 (MAP2)+cells), and apoptosis (caspase 3 (CC3)+cells). Co-incubation with EPA and DHA prevented the decrease in MAP2 + cells caused by IFN-alpha (from −36% to + 12%, p 0.05, with EPA and to + 6%, p 0.05, with DHA) and IL-1beta (from −37% to + 5%, p 0.05, with EPA and to + 2%, p 0.001, with DHA). However, DHA but not EPA was able to prevent the increase in CC3 + cells caused by IL-1beta (from + 50% to −5%, p 0.05) and IFN-alpha(from + 5% to −2%, p 0.05). IL-6 did not affect DCX + and MAP2 + cells, but its detrimental effect on CC3 + cells was fully prevented only by EPA(from + 50% to −5%, p 0.05). Further characterization of the underlying mechanisms of EPA and DHA action will be of benefit towards future personalized medicine approach for patients with depression.