The development of fetal brain is influenced by nutrients such as docosahexaenoic acid (DHA, 22:6) and choline. Phosphatidylethanolamine-N-methyltransferase (PEMT) catalyzes the biosynthesis of phosphatidylcholine (PtdCho) from phosphatidylethanolamine that is enriched in DHA and many humans have functional genetic polymorphisms in the PEMT gene. Previously, it was reported that Pemt-/- mice have altered hippocampal development.

The present study explores whether abnormal PtdCho biosynthesis causes altered incorporation of DHA into membranes, thereby influencing brain development, and determines whether supplemental dietary DHA can reverse some of these changes. Pregnant C57BL/6 wild type (WT) and Pemt-/- mice were fed control diet, or diet supplemented with 3g/kg DHA, from gestational day 11-17. Brains from embryonic day 17 fetuses derived from Pemt-/- dams fed the control diet had 25-50% less phospholipid-DHA as compared to WT (p<0.05). Also, they had 60% more neural progenitor cell proliferation (p<0.05), 60% more neuronal apoptosis (p<0.01) and 30% less calretinin expression (p<0.05; a marker of neuronal differentiation) in the hippocampus compared to WT. The DHA supplemented diet increased fetal brain Pemt-/- phospholipid-DHA to WT levels, and abrogated the neural progenitor cell proliferation and apoptosis differences. While this diet did not change proliferation in the WT group, it halved the rate of apoptosis (p<0.05). In both genotypes, the DHA supplemented diet increased calretinin expression 2-fold (p<0.05).

These results suggest that the changes in hippocampal development in the Pemt-/- mouse could be mediated by altered DHA incorporation into membrane phospholipids, and that maternal dietary of DHA can influence fetal brain development.

PMID 19889625

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