American Journal of Obstetrics & Gynecology
Volume 194, Issue 3 , Pages 681-686, March 2006

Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA and GABA receptors

  • Laura Toso, MD

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
    • Corresponding Author InformationReprint requests: Laura Toso, MD, UPDN, NICHD, NIH and NIAAA, NIH, Bldg 9, Room 1W125, 9 Memorial Drive MSC 0925, Bethesda, MD 20892-0925.
    • ,
  • Sarah H. Poggi, MD

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • Department of Obstetrics and Gynecology, INOVA Hospital, Alexandria, VA
    • ,
  • Robin Roberson

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • ,
  • Jade Woodard

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • ,
  • Jane Park

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • ,
  • Daniel Abebe

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development
    • ,
  • Catherine Y. Spong, MD

      Affiliations

    • Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development

Received 7 December 2005; received in revised form 5 January 2006; accepted 7 January 2006.

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 GABAAα5.

Study design

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 GABAAα5 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 GABAAα5 decrease (P < .01) on gestational day 18. In the adult, the peptides prevented NR2B down-regulation (P = .01) and NR2A up-regulation (P < .001).

Conclusion

VIP-related peptides prevented alcohol-induced changes in NR2B, NR2A, and GABAAα5. This may explain, at least in part, the peptides' prevention of alcohol-induced learning deficits.

Key words: Fetal alcohol syndrome, Alcohol, NMDA, GABA, Learning, Neurotrophic factors

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 Presented at the 26th Annual Meeting of the Society for Maternal Fetal Medicine, Miami, FL, January 30-February 4, 2006.This work was supported by the Division of Intramural Research of National Institute of Child and Human Development.

PII: S0002-9378(06)00046-9

doi:10.1016/j.ajog.2006.01.003

American Journal of Obstetrics & Gynecology
Volume 194, Issue 3 , Pages 681-686, March 2006

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