Effects of postnatal ethanol exposure on neurotrophic factors and signal transduction pathways in rat brain.
Exposure to ethanol during development induces severe brain damage, resulting in a number of CNS dysfunctions including microencephaly and mental retardation. Potential targets of ethanol-induced neurotoxicity include neurotrophic factors and their signal transduction pathways. In the present study, rat pups were given ethanol at the dose of 5 g kg(-1) via gavage from postnatal day (PND) 5 to 8, and mRNA expression of nerve growth-factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophic factor-3 (NT-3) in the cerebral cortex was examined, with attention to signal transduction, on PND 8. The mRNA level of BDNF was decreased by ethanol while those of NGF or NT-3 were not changed. Brain weights were decreased and the levels of phospho-MAPK, phospho-p70S6K and phospho Akt were decreased while phosphor-PKCzeta and phospho-CREB remained unchanged. These results suggest that BDNF and its related signal pathways involving Akt, MAPK and p70S6K are potential targets of ethanol-induced developmental neurotoxicity.
Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd., 3-1-98 Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan.
Vittorio
V
Fattori
Shin-ichi
S
Abe
Kumiko
K
Kobayashi
Lucio G
LG
Costa
Ryozo
R
Tsuji
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D009414:Nerve Growth Factors; D000431:Ethanol; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020929:Mitogen-Activated Protein Kinase Kinases