Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus

Nutrients. 2014 Oct 14;6(10):4200-17. doi: 10.3390/nu6104200.

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.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation*
  • DNA Methylation*
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / metabolism
  • Dietary Supplements
  • Doublecortin Protein
  • Female
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Gene-Environment Interaction
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Insulin-Like Growth Factor II / genetics
  • Maternal Nutritional Physiological Phenomena*
  • Nestin / genetics
  • Neural Stem Cells / cytology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Insulin / genetics
  • Weaning

Substances

  • Dcx protein, rat
  • Dietary Proteins
  • Doublecortin Protein
  • Glial Cell Line-Derived Neurotrophic Factor
  • Igf2 protein, rat
  • Nestin
  • Insulin-Like Growth Factor II
  • Receptor, Insulin