title: Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus.
abstract: Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. valerie.amarger@univ-nantes.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Amarger
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. angele.lecouillard@oniris-nantes.fr.
authors.forename: Angèle
authors.initials: A
authors.lastname: Lecouillard
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. laure.ancellet@elementa-ingredients.com.
authors.forename: Laure
authors.initials: L
authors.lastname: Ancellet
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. isabelle.grit@univ-nantes.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Grit
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. blandine.castellano@univ-nantes.fr.
authors.forename: Blandine
authors.initials: B
authors.lastname: Castellano
authors.affiliation: Plateforme MicroPICell, SFR Santé, 44093 Nantes, France. philippe.hulin@nantes.inserm.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hulin
authors.affiliation: INRA-University of Nantes, UMR1280, 44093 Nantes, France. patricia.parnet@univ-nantes.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Parnet
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D019175:DNA Methylation; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000378:metabolism; D019587:Dietary Supplements; D000089662:Doublecortin Protein; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D039382:Maternal Nutritional Physiological Phenomena; D064231:Nestin / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics; D014886:Weaning
chemical_list: C000714848:Dcx protein, rat; D004044:Dietary Proteins; D000089662:Doublecortin Protein; D051100:Glial Cell Line-Derived Neurotrophic Factor; C000599313:Igf2 protein, rat; D064231:Nestin; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin