Prenatal ethanol exposure persistently impairs NMDA receptor-dependent activation of extracellular signal-regulated kinase in the mouse dentate gyrus

J Neurochem. 2009 Jun;109(5):1311-23. doi: 10.1111/j.1471-4159.2009.06049.x. Epub 2009 Mar 20.


The dentate gyrus (DG) is the central input region to the hippocampus and is known to play an important role in learning and memory. Previous studies have shown that prenatal alcohol is associated with hippocampal-dependent learning deficits and a decreased ability to elicit long-term potentiation (LTP) in the DG in adult animals. Given that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade by NMDA receptors is required for various forms of learning and memory, as well as LTP, in hippocampal regions, including the DG, we hypothesized that fetal alcohol-exposed adult animals would have deficits in hippocampal NMDA receptor-dependent ERK1/2 activation. We used immunoblotting and immunohistochemistry techniques to detect NMDA-stimulated ERK1/2 activation in acute hippocampal slices prepared from adult fetal alcohol-exposed mice. We present the first evidence linking prenatal alcohol exposure to deficits in NMDA receptor-dependent ERK1/2 activation specifically in the DG of adult offspring. This deficit may account for the LTP deficits previously observed in the DG, as well as the life-long cognitive deficits, associated with prenatal alcohol exposure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Butadienes / pharmacology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / metabolism*
  • Dizocilpine Maleate / pharmacology
  • Embryo, Mammalian
  • Enzyme Activation / drug effects
  • Ethanol*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal / methods
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Nitriles / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / drug effects
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Butadienes
  • Excitatory Amino Acid Antagonists
  • Nitriles
  • Receptors, N-Methyl-D-Aspartate
  • U 0126
  • Ethanol
  • Dizocilpine Maleate
  • 2-amino-5-phosphopentanoic acid
  • Mitogen-Activated Protein Kinase 1
  • Valine