Dietary Polyunsaturated Fatty Acids in Gestation Alter Fetal Cortical Phospholipids, Fatty Acids and Phosphatidylserine Synthesis

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Abstract
Docosahexaenoic acid (DHA; 22:6 n–3) is high in brain phosphatidylserine (PS) and phosphatidylethanolamine (PE), but low in phosphatidylcholine (PC). PS is synthesized from PE or PC by exchange of ethanolamine or choline for serine. PS can be decarboxylated to PE, and PC is synthesized from PE by phosphatidylethanolamine N-methyltransferase (PEMT). We characterized the perinatal changes in rat brain cortex phospholipids and metabolism and determined if maternal dietary n–3 fatty acid intake alters newborn brain cortex phospholipids, serine base exchange, PS decarboxylase or PEMT activities. PE became increasingly predominant, with an increase in the cortex PC/PE ratio from 2:1 at gestation day 19 to 1:1 at postnatal day 20. DHA increased and n–6 docosapentaenoic acid (DPA; 22:5 n–6) decreased in all phospholipids during development. [3H]serine incorporation into PS was higher in the fetal than neonatal brain cortex. Newborn rats of dams fed an n–3 fatty acid-deficient diet with 0.02% energy alpha-linolenic acid (ALA; 18:3 n–3) had approximately 50% lower DHA and higher DPA in cortex PE, PS and PC than newborns of rats fed a control diet with 1.5% energy ALA. [3H]serine incorporation into PS was significantly lower in the brain cortex of n–3 fatty acid-deficient than control newborns. n–3 Fatty acid deficiency had no effect on newborn brain PEMT or serine decarboxylase activities. These studies show that maternal dietary n–3 fatty acid deprivation impairs fetal brain DHA accretion and PS metabolism; altered PS metabolism may change release of lipid mediators and neurotransmitter precursors important in brain function.