Survival and proliferation in developing neuroblasts in cultures derived from embryos treated with ethanol during early neuroembryogenesis: effects attenuated by somatostatin.
Ethanol exerts profound effects both in ovo and in culture on neuronal phenotypic expression. In order to define more directly the neuronal growth parameters sensitive to the neurotoxic effects of ethanol, embryos were exposed to ethanol (10 mg/50 microliters/day) or saline (control) at embryonic days 1 and 2; neuron-enriched cultures prepared from these treated embryos at 3 days of embryonic age. Cultures from both groups were labeled with [3H]thymidine and assessed for effects on neuronal survival and proliferation in culture. Treatment of embryos with ethanol in ovo resulted in a marked enhancement in normal neuronal death in culture with no significant effect on proliferation. Whereas somatostatin (SRIF) had no effect on normally occurring neuronal death in control cultures, addition of SRIF (100 nM) to the culture medium attenuated the ethanol-induced neuronal cell death. Videometric analysis revealed that pretreatment of embryos with ethanol resulted in formation of more and larger aggregates as compared with controls, an effect that was augmented by addition of SRIF to the medium. The most profound effect of ethanol on growth patterns was observed in neurite outgrowth showing a marked reduction in both neurite number and length in embryos pretreated with ethanol. SRIF enhanced neurite outgrowth (neurite number and length) in cultures derived from ethanol-treated embryos. These results suggest that the ethanol-induced deficits in neuronal survival and morphology are reversible. We conclude that SRIF may enhance neuronal survival by promoting neuritic outgrowth, thus establishing the essential target cell contacts necessary for cell survival.
Kentroti
S
S
Department of Pharmacology, University of Colorado, School of Medicine, Denver 80262.
Vernadakis
A
A
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects*; D004625:Embryo, Nonmammalian; D000431:Ethanol / Q000494:pharmacology*; D009420:Nervous System / Q000196:embryology*; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*
D000431:Ethanol; D013004:Somatostatin