Perinatal exposure to alcohol disturbs spatial learning and glutamate transmission-related gene expression in the adult hippocampus

Eur J Neurosci. 2011 Aug;34(3):457-68. doi: 10.1111/j.1460-9568.2011.07776.x. Epub 2011 Jul 4.

Abstract

Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances accompanied by disturbed synaptic plasticity. Here we studied the long-term behavioral consequences of PEA and investigated glutamate transmission-related genes in a longitudinal fashion. After delivery, female Wistar rats and their pups were exposed to ethanol until postnatal day (PD)8 in vapor chambers. At the age of 5 months, the animals were behaviorally characterized. At both PD8 and after the behavioral testing we examined the expression of the vesicular glutamate transporter 1 and excitatory amino acid transporter (EAAT)1-4, as well as the N-methyl-D-aspartate receptor subunits (NR)1 and 2A-D, and in parallel receptor binding using (3) H-dizocilpine maleate receptor autoradiography. We found highly significant reductions of body weight and length following PEA in pups at PD8. These alterations disappeared in adulthood, when no changes of motor activity and only subtle differences of anxiety-related behavior were observed. It also did not affect T-maze learning, but had a pronounced effect on hippocampus-dependent spatial learning (Morris water maze testing). This specific learning deficit was accompanied by a dysregulation in hippocampal gene expression (significant induction of vesicular glutamate transporter 1, EAAT1, EAAT3, NR2A, 2B, 2C and 2D). Most of the examined genes turned out to be dysregulated to a higher degree at the age of 5 months. We therefore conclude that perinatal ethanol toxicity alters the plasticity of neurodevelopment and the regulation of glutamatergic gene expression, which may result in specific hippocampus-dependent learning deficits in adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Ethanol / blood
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Transporter 1 / genetics
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Excitatory Amino Acid Transporter 3 / genetics
  • Excitatory Amino Acid Transporter 3 / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • Humans
  • Learning Disabilities / chemically induced
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Neuropsychological Tests
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology
  • Vesicular Glutamate Transport Protein 1 / genetics
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 3
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate
  • Slc17a7 protein, rat
  • Slc1a1 protein, rat
  • Slc1a3 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Ethanol
  • Glutamic Acid