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 growth 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 mitogen-activated/extracellular signal-regulated protein kinase (MAPK/ERK) activation 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 pups and activation and cellular localization was determined with immunofluorescence combined with confocal microscopy. EtOH decreased ERK activation in vivo and decreased nuclear translocation of BDNF-stimulated ERK in situ. These data suggest EtOH-induced inhibition of growth factor signaling may contribute to the development of fetal alcohol syndrome and alcohol-related birth defects.
Davis
M I
MI
Department of Biomedical Sciences, School of Public Health at the University at Albany, NY, USA. midavis@ufbi.ufl.edu
Szarowski
D
D
Turner
J N
JN
Morrisett
R A
RA
Shain
W
W
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D000431:Ethanol; D020928:Mitogen-Activated Protein Kinases