In vivo ethanol decreases phosphorylated MAPK and p70S6 kinase in the developing rat brain.
Exposure to ethanol during pregnancy is detrimental to fetal development, and individuals affected by the fetal alcohol syndrome present a number of CN system dysfunctions including microencephaly and mental retardation. Recently, it has been suggested that ethanol-induced inhibition of glial cell proliferation may be relevant in the causation of microencephaly. In this study, we measured the developmental changes of MAPK (ERKl/2) and p70S6 kinase, which are considered to play a prominent role in cell proliferation, and their phosphorylated proteins in rat brain, and examined the effects of in vivo ethanol administration. MAPK and phospho-MAPK increased gradually after birth, and reached adult levels on postnatal day 21. In contrast, levels of both p70S6 kinase and phospho-p70S6 kinase decreased after birth. Exposure to ethanol (2-6 g/kg, from postnatal day 4 to 7) had no effects on MAPK or p70S6 kinase levels, but caused a dose-dependent decrease of both phosphoproteins. These results suggest that phosphorylation of MAPK and p70S6 kinase may represent relevant targets for the developmental neurotoxicity of ethanol, and may be involved in microencephaly.
Tsuji
Ryozo
R
Department of Environmental Health, University of Washington, 4225 Roosevelt Way NE, #100 Seattle, WA 98105-6099, USA.
Guizzetti
Marina
M
Costa
Lucio G
LG
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*
D002492:Central Nervous System Depressants; D000431:Ethanol; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020929:Mitogen-Activated Protein Kinase Kinases