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.
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.


METHODS
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.


CONCLUSIONS
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.
Toso
Laura
L
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
Roberson
Robin
R
Abebe
Daniel
D
Spong
Catherine Y
CY
D000818:Animals; D002971:Cleft Lip / Q000139:chemically induced*; D002972:Cleft Palate / Q000139:chemically induced*; D000431:Ethanol / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology*; D007859:Learning Disabilities / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology*
C546273:GABRB3 protein, human; C546270:Gabrb3 protein, mouse; D009842:Oligopeptides; D011963:Receptors, GABA-A; C502410:seryl-alanyl-leucy-leucyl-arginyl-seryl-isoleucyl-prolyl-alanine; D000431:Ethanol; C425904:davunetide