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.
Original language | English (US) |
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Pages (from-to) | 259.e1-259.e5 |
Journal | American journal of obstetrics and gynecology |
Volume | 196 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2007 |
Externally published | Yes |
Keywords
- N-methyl-D-aspartate (NMDA)
- fetal alcohol syndrome
- learning
- mouse
- γ-aminobutyric acid A (GABA)
ASJC Scopus subject areas
- Obstetrics and Gynecology