Neuroprotective peptides prevent some alcohol-induced alteration in γ-aminobutyric acid A-β3, which plays a role in cleft lip and palate and learning in fetal alcohol syndrome

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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 γ-aminobutyric acid A (GABA) receptor subunit GABAβ3 plays a critical role for nervous system and palate development. Our objective was to determine whether the neuropeptides prevented alcohol-induced damage through GABAβ3.

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 μg). 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 GABAβ3 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 GABAβ3 in the embryos (P ≤ .01); this decrease was prevented by the peptides (P = .01). GABAβ3 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 GABAβ3 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.

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