title: Perinatal exposure to alcohol disturbs spatial learning and glutamate transmission-related gene expression in the adult hippocampus.
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.
authors: Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, University of Heidelberg, PO Box 12 21 20, D-68072 Mannheim, Germany.
authors: Mathias
authors: M
authors: Zink
authors: Thomas
authors: T
authors: Ferbert
authors: Stefanie T
authors: ST
authors: Frank
authors: Patricia
authors: P
authors: Seufert
authors: Peter J
authors: PJ
authors: Gebicke-Haerter
authors: Rainer
authors: R
authors: Spanagel
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007859:Learning Disabilities / Q000139:chemically induced; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C493466:Slc17a7 protein, rat; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D000431:Ethanol; D018698:Glutamic Acid