3-DAY EXPOSURE TO LOW-DOSE ETHANOL ALTERS GUANINE-NUCLEOTIDE-BINDING PROTEIN EXPRESSION IN THE DEVELOPING RAT HIPPOCAMPUS

Alcohol-related birth defects result from acute and chronic insults th at perturb sequential developmental programs. The molecular targets of EtOH include G-protein coupled signal transduction pathways. In order to test the hypothesis that G-proteins are involved in EtOH-induced h ippocampal teratogenesis, rat pups were administered 3.3 g/kg . day of EtOH on postnatal days (PN) 5 to 7 using the pup-in-a-cup model of th ird trimester ''binge'' exposure. This exposure paradigm produced a se lective 40% decrease in the 52 kDa isoform of the stimulatory form of the heterotrimeric guanine nucleotide binding protein (G(alpha s)) in the hippocampus on PN 7 with no significant changes in the levels of G (alpha i) or G(alpha o). Immunohistochemistry demonstrated that this d ecrease occurred in the somas of both hippocampal pyramidal cells and granule cells of the dentate gyrus. Computer-assisted cell counting in dicates that this decrease was not due to pyramidal cell death on PN 7 . Northern and slot blot analysis demonstrated a 30% decrease in G(alp ha s) messenger RNA in the hippocampus. These results suggest that EtO Hs teratogenic effects in the hippocampus may involve disruption of G( alpha s)-coupled signal transduction pathways, which are critical for normal synaptogenesis, neurotransmitter signaling and the integration of these signals with growth factor signaling pathways.