title: Dietary docosahexaenoic acid supplementation modulates hippocampal development in the Pemt-/- mouse.
abstract: 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 from phosphatidylethanolamine 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 phosphatidylcholine 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 a control diet, or a diet supplemented with 3 g/kg of DHA, from gestational day 11 to 17. Brains from embryonic day 17 fetuses derived from Pemt(-/-) dams fed the control diet had 25-50% less phospholipid-DHA as compared with 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 with WT. The DHA-supplemented diet increased fetal brain Pemt(-/-) phospholipid-DHA to WT levels, and abrogated the neural progenitor cell proliferation and apoptosis differences. Although 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 DHA can influence fetal brain development.
authors.affiliation: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Kerry-Ann
authors.initials: KA
authors.lastname: da Costa
authors.forename: Kiranmai S
authors.initials: KS
authors.lastname: Rai
authors.forename: Corneliu N
authors.initials: CN
authors.lastname: Craciunescu
authors.forename: Komal
authors.initials: K
authors.lastname: Parikh
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Mehedint
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sanders
authors.forename: Audrey
authors.initials: A
authors.lastname: McLean-Pottinger
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology*; D006624:Hippocampus / Q000196:embryology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050941:Phosphatidyl-N-Methylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D010743:Phospholipids; D004281:Docosahexaenoic Acids; D050941:Phosphatidyl-N-Methylethanolamine N-Methyltransferase