Prenatal choline supplementation advances hippocampal development and enhances MAPK and CREB activation

FASEB J. 2004 Mar;18(3):545-7. doi: 10.1096/fj.03-0877fje. Epub 2004 Jan 8.


Choline is an essential nutrient for animals and humans. Previous studies showed that supplementing the maternal diet with choline during the second half of gestation in rats permanently enhances memory performance of the adult offspring. Here we show that prenatal choline supplementation causes a 3-day advancement in the ability of juvenile rats to use relational cues in a water maze task, indicating that the treatment accelerates hippocampal maturation. Moreover, phosphorylation and therefore activation of hippocampal mitogen-activated protein kinase (MAPK) and cAMP-response element binding protein (CREB) in response to stimulation by glutamate, N-methyl-D-aspartate, or depolarizing concentrations of K+ were increased by prenatal choline supplementation and reduced by prenatal choline deficiency. These data provide the first evidence that developmental plasticity of the hippocampal MAPK and CREB signaling pathways is controlled by the supply of a single essential nutrient, choline, during fetal development and point to these pathways as candidate mechanisms for the developmental and long-term cognitive enhancement induced by prenatal choline supplementation.

MeSH terms

  • Animals
  • Choline / administration & dosage
  • Choline / pharmacology*
  • Choline Deficiency / metabolism
  • Choline Deficiency / psychology
  • Cues
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Female
  • Glutamic Acid / pharmacology
  • Hippocampus / embryology*
  • Hippocampus / physiology
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Maze Learning / drug effects*
  • Memory Disorders / etiology
  • Mitogen-Activated Protein Kinases / metabolism*
  • N-Methylaspartate / pharmacology
  • Phosphorylation / drug effects
  • Potassium / pharmacology
  • Pregnancy
  • Pregnancy Complications / metabolism
  • Prenatal Exposure Delayed Effects*
  • Protein Processing, Post-Translational / drug effects
  • Rats
  • Reaction Time
  • Spatial Behavior


  • Cyclic AMP Response Element-Binding Protein
  • Glutamic Acid
  • N-Methylaspartate
  • Mitogen-Activated Protein Kinases
  • Choline
  • Potassium