Neuroprotective peptides prevent some alcohol-induced alteration in gamma-aminobutyric acid A-beta3, which plays a role in cleft lip and palate and learning in fetal alcohol syndrome.

Abstract

OBJECTIVE:

Prenatal alcohol exposure affects 1 in 100 births in the United States and results in craniofacial dysmorphologic condition and learning disabilities. In a model for fetal alcohol syndrome, neuroprotective peptides prevented fetal death and learning deficits. The gamma-aminobutyric acid A (GABA) receptor subunit GABAbeta3 plays a critical role for nervous system and palate development. Our objective was to determine whether the neuropeptides prevented alcohol-induced damage through GABAbeta3.

STUDY DESIGN:

With a model for fetal alcohol syndrome, timed pregnant C57B16/J mice were treated on gestational day 8 with alcohol (25% alcohol) or control (saline solution) or alcohol plus peptides NAPVSIPQ + SALLRSIPA (NAP + SAL; 20 microg). Embryos were harvested at 6 and 24 hours and 10 days after treatment. Adult males were tested for learning on the Morris water maze, and their brains were dissected. With samples from at least 3 litters per time point, calibrator-normalized relative real-time polymerase chain reaction was performed for GABAbeta3 with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistical analysis included analysis of variance and Fisher protected least significant difference.

RESULTS:

Twenty-four hours and 10 days after treatment, alcohol decreased GABAbeta3 in the embryos (P < or = .01); this decrease was prevented by the peptides (P = .01). GABAbeta3 was higher in alcohol treated adult brains respect to the controls (P = .002); this rise was not prevented by the peptides.

CONCLUSION:

Treatment with the neuropeptides NAPVSIPQ and SALLRSIPA prevented the alcohol-induced decline in GABAbeta3 expression 10 days after alcohol exposure. Because palate formation continues through E18, NAPVSIPQ and SALLRSIPA may be beneficial for the prevention of cleft lip and palate.

• Authors: Laura Toso, Robin Roberson, Daniel Abebe, Catherine Y Spong
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 196 Issue 3 Pg. 259.e1-5 (Mar 2007) ISSN: 1097-6868 [Electronic] United States
• PMID: 17346546 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• GABRB3 protein, human
• Gabrb3 protein, mouse
• Oligopeptides
• Receptors, GABA-A
• seryl-alanyl-leucy-leucyl-arginyl-seryl-isoleucyl-prolyl-alanine
• Ethanol
• davunetide

Topics

• Animals
• Cleft Lip (chemically induced)
• Cleft Palate (chemically induced)
• Ethanol (adverse effects, antagonists & inhibitors)
• Female
• Fetal Alcohol Spectrum Disorders (etiology)
• Learning Disabilities (chemically induced)
• Mice
• Mice, Inbred C57BL
• Oligopeptides (pharmacology)
• Pregnancy
• Receptors, GABA-A (drug effects, physiology)