DHA enhances the noradrenaline release by SH-SY5Y cells

Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and arachidonic acid (AA), are the main components of the phospholipids, in cerebral membranes. A dietary-induced cerebral DHA deficit results in altered behaviour and neurotransmission in rodents. To determine whether PUFA were acting on the neurotransmitter release machinery, we measured the release of [ 3H]-noradrenaline (NA) from SH-SY5Y neuroblastoma cells with modified PUFA membrane contents and from cells incubated with medium containing high DHA or AA. The membranes of cells incubated with 70 μM DHA for 3 days had 7.6-times more DHA in their ethanolamine glycerophospholipids, while the membranes of cells incubated with AA had 40% less. Incorporation of DHA enhanced basal [ 3H]-NA release (25%, p < 0.05), but not KCl-evoked [ 3H]-NA release. Brief incubation with DHA during vesicle mobilization also strongly increased [3H]-NA release. AA had no effect. The genes encoding for the calcium sensor synaptotagmin1, and for the two SNARE complex proteins syntaxin1A and synaptobrevin1 were not affected by PUFA incorporation, as indicated by assays for specific mRNAs and proteins. Thus both a high membrane DHA content and free DHA in the medium enhance the release of [ 3H]-NA from SH-SY5Y cells. This suggests that brain membrane DHA influences exocytosis, which then regulates neurotransmission.