Docosahexaenoic acid decreases apoptosis of hippocampal neurons

Docosahexaenoic acid (DHA) has been shown to prevent neuronal apoptosis through facilitating Akt translocation to plasma membrane. Although PS accumulation by DHA is a key event in this protection, the effect of DHA on the apoptotic progression or intracellular distribution of PS remains largely unknown. In this study, we evaluated the protective effect of DHA in hippocampal primary neurons along with characterization of apoptotic processes and PS intracellular distribution. E‐18 rat hippocampal cells were grown in chemically defined medium supplemented with or without 2uM DHA, Oleic or Arachidonic acid for 4 days. Basal apoptosis evaluated by immunostaining and TUNEL assay indicated that DHA decreased apoptosis most significantly (by 50%) in comparison to other fatty acids. Caspase‐3 activation preceded PS externalization which was followed by nuclear condensation regardless of DHA supplementation. When Neuro 2A and hippocampal neurons expressed GFP‐AnnexinV, a specific PS‐binding protein, and were stimulated with calcium ionophore, translocation of Annexin V to the plasma and nuclear membranes was observed from cytoplasm and nucleoplasm, respectively. In conclusion, we demonstrate that DHA has a protective role in hippocampal apoptosis without affecting progression of apoptosis, by accumulating PS specifically in the inner leaflet of the plasma membrane and in the nuclear envelope.