title: Perinatal α-linolenic acid availability alters the expression of genes related to memory and to epigenetic machinery, and the Mecp2 DNA methylation in the whole brain of mouse offspring.
abstract: Many animal and human studies indicated that dietary ω-3 fatty acids could have beneficial roles on brain development, memory, and learning. However, the exact mechanisms involved are far from being clearly understood, especially for α-linolenic acid (ALA), which is the precursor for the ω-3 elongation and desaturation pathways. This study investigated the alterations induced by different intakes of flaxseed oil (containing 50% ALA), during gestation and lactation, upon the expression of genes involved in neurogenesis, memory-related molecular processes, and DNA methylation, in the brains of mouse offspring at the end of lactation (postnatal day 19, P19). In addition, DNA methylation status for the same genes was investigated. Maternal flaxseed oil supplementation during lactation increased the expression of Mecp2, Ppp1cc, and Reelin, while decreasing the expression of Ppp1cb and Dnmt3a. Dnmt1 expression was decreased by postnatal flaxseed oil supplementation but this effect was offset by ALA deficiency during gestation. Mecp2 DNA methylation was decreased by maternal ALA deficiency during gestation, with a more robust effect in the lactation-deficient group. In addition, linear regression analysis revealed positive correlations between Mecp2, Reelin, and Ppp1cc, between Gadd45b, Bdnf, and Creb1, and between Egr1 and Dnmt1, respectively. However, there were no correlations, in any gene, between DNA methylation and gene expression. In summary, the interplay between ALA availability during gestation and lactation differentially altered the expression of genes involved in neurogenesis and memory, in the whole brain of the offspring at the end of lactation. The Mecp2 epigenetic status was correlated with ALA availability during gestation. However, the epigenetic status of the genes investigated was not associated with transcript levels, suggesting that either the regulation of these genes is not necessarily under epigenetic control, or that the whole brain model is not adequate for the exploration of epigenetic regulation in the context of this study.
authors.affiliation: Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA.
authors.forename: Fuli
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lupu
authors.affiliation: Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA. Electronic address: Mihai_Niculescu@unc.edu.
authors.forename: Mihai D
authors.initials: MD
authors.lastname: Niculescu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D000091042:Reelin Protein; D013223:Statistics as Topic; D017962:alpha-Linolenic Acid / Q000633:toxicity*; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D051766:Early Growth Response Protein 1; D051783:Methyl-CpG-Binding Protein 2; D000091042:Reelin Protein; D017962:alpha-Linolenic Acid; C486109:Egr1 protein, mouse; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C000717127:RELN protein, human; C000717128:Reln protein, mouse
keywords: Brain development; DNA methylation; Flaxseed oil; Lactation; Perinatal nutrition; α-Linolenic acid