Laura Toso1, Robin Roberson, Daniel Abebe, Catherine Y Spong. 1. Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. tosol@mail.nih.gov
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.
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; Andrea Johnson; Stephanie Bissell; Robin Roberson; Daniel Abebe; Catherine Y Spong Journal: Am J Obstet Gynecol Date: 2007-09 Impact factor: 8.661