Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA and GABA receptors.
OBJECTIVE
Vasoactive intestinal peptide (VIP)-related peptides prevented the learning deficit in the offspring in a model for fetal alcohol syndrome. We evaluated whether the mechanism of the peptide protection included NR2B, NR2A, and GABAAalpha5.


METHODS
Timed, pregnant C57BL6/J mice were injected on gestational day 8 with alcohol (0.03 mL/kg), placebo, or alcohol plus peptides. Embryos were harvested after 6 hours, 24 hours, and on gestational day 18. Some of the litters were allowed to deliver, and the adult brains harvested after the offspring were tested for learning. Calibrator-normalized relative real-time polymerase chain reaction (PCR) was performed using primers for NR2B, NR2A, and GABAAalpha5 with GAPDH standardization. Statistic: analysis of variance (ANOVA) and Fisher PLSD, P < .05 was considered significant.


RESULTS
In the embryo, the peptides prevented NR2B rise (P < .001) at 6 hours, NR2B down-regulation (P = .002), and GABAAalpha5 decrease (P < .01) on gestational day 18. In the adult, the peptides prevented NR2B down-regulation (P = .01) and NR2A up-regulation (P < .001).


CONCLUSIONS
VIP-related peptides prevented alcohol-induced changes in NR2B, NR2A, and GABAAalpha5. This may explain, at least in part, the peptides' prevention of alcohol-induced learning deficits.
Toso
Laura
L
Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development, National Institutes of Health, Bethesda, MD 20892-0925, USA. laura_toso@hotmail.com
Poggi
Sarah H
SH
Roberson
Robin
R
Woodard
Jade
J
Park
Jane
J
Abebe
Daniel
D
Spong
Catherine Y
CY
D000818:Animals; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders; D007859:Learning Disabilities / Q000209:etiology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000627:therapeutic use*; D011247:Pregnancy; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
C496250:Gabra5 protein, mouse; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009842:Oligopeptides; D021122:Protein Subunits; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C410622:activity-dependent neurotrophic factor; C425904:davunetide