In vivo activation and in situ BDNF-stimulated nuclear translocation of mitogen-activated/extracellular signal-regulated protein kinase is inhibited by ethanol in the developing rat hippocampus

In order to test the hypothesis that ethanol (EtOH)-induced changes in grow th factor signal transduction contribute to the teratogenic effects of EtOH in the developing brain, neonatal rat pups were administered a single dose of EtOH during the brain growth spurt (5 days of age, PN5). Hippocampal mi togen-activated/extracellular signal-regulated protein kinase (MAPK/ERK) ac tivation was analyzed one to 6 h after exposure by electrophoretic-mobility shift assay combined with western blot. Brain-Derived Neurotrophic Factor (BDNF) was used to stimulate ERK in hippocampal slices prepared from PN5 pu ps and activation and cellular localization was determined with immunofluor escence combined with confocal microscopy. EtOH decreased ERK activation in vivo and decreased nuclear translocation of BDNF-stimulated ERK in situ. T hese data suggest EtOH-induced inhibition of growth factor signaling may co ntribute to the development of fetal alcohol syndrome and alcohol-related b irth defects. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.