title: Reversal of alcohol-induced learning deficits in the young adult in a model of fetal alcohol syndrome.
abstract: OBJECTIVE
  To evaluate whether treatment with neuroprotective peptides to young adult mice prenatally exposed to alcohol reverses alcohol-induced learning deficits in a mouse model of fetal alcohol syndrome, whether the mechanism involves the N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid type A (GABAA) receptors, and whether it is related to glial cells.
  
  
  METHODS
  C57Bl6/J mice were treated with alcohol (0.03 ml/g) or placebo on gestational day 8. On day 40, male mice exposed to alcohol in utero were treated daily for 10 days with D-NAPVSIPQ and D-SALLRSIPA (n=20) or placebo (n=13); and control offspring were treated with placebo (n=46), with the treatment blinded. Learning evaluation began after 3 days using the Morris watermaze and the T-maze. The hippocampus, cortex, and cerebellum were isolated. Expression of NR2A, NR2B, GABAAbeta3, GABAAalpha5, vasoactive intestinal peptide (VIP), activity-dependent neuroprotective protein, and glial fibrillary acidic protein was measured using calibrator-normalized relative real-time polymerase chain reaction. Statistical analysis included analysis of variance and Fisher's protected least significant difference.
  
  
  RESULTS
  Treatment with D-NAPVSIPQ and D-SALLRSIPA reversed the alcohol-induced learning deficit in both learning tests as well as the NR2A and NR2B down-regulation in the hippocampus and the up-regulation of NR2A in the cortex and NR2B in the cortex and cerebellum (all P<.05). No significant differences were found in GABAA expression. Moreover, the peptides changed activity-dependent neuroprotective protein expression in the cortex (P=.016) but not the down-regulation of VIP (P=.883), probably because the peptides are downstream from VIP.
  
  
  CONCLUSIONS
  Alcohol-induced learning deficit was reversed and expression of NR2A and NR2B was restored in the hippocampus and cortex of young adult mice treated with D-NAPVSIPQ and D-SALLRSIPA. Given the role of NMDA receptors in learning, this may explain in part the mechanism of prevention of alcohol-induced learning deficits by D-NAPVSIPQ and D-SALLRSIPA.
authors.affiliation: From the Unit on Perinatal and Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; and the Division of Maternal Fetal Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Incerti
authors.forename: Joy
authors.initials: J
authors.lastname: Vink
authors.forename: Robin
authors.initials: R
authors.lastname: Roberson
authors.forename: Lorraine
authors.initials: L
authors.lastname: Wood
authors.forename: Daniel
authors.initials: D
authors.lastname: Abebe
authors.forename: Catherine Y
authors.initials: CY
authors.lastname: Spong
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000523:psychology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C526732:SALLRSIPA; D014660:Vasoactive Intestinal Peptide; C425904:davunetide