Three-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 that 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 hippocampal 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 third trimester "binge" exposure. This exposure paradigm produced a selective 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 decrease occurred in the somas of both hippocampal pyramidal cells and granule cells of the dentate gyrus. Computer-assisted cell counting indicates that this decrease was not due to pyramidal cell death on PN 7. Northern and slot blot analysis demonstrated a 30% decrease in G alpha s messenger RNA in the hippocampus. These results suggest that EtOHs 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.
Davis-Cox
M I
MI
Wadsworth Center, New York State Department of Health, Albany, USA.
Fletcher
T L
TL
Turner
J N
JN
Szarowski
D
D
Shain
W
W
D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D000431:Ethanol / Q000633:toxicity*; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D012333:RNA, Messenger; D000431:Ethanol; D000242:Cyclic AMP; D019204:GTP-Binding Proteins