Altered Pattern of Na,K-ATPase Activity and mRNA During Chronic Alcohol Consumption by Juvenile and Adolescent Rats
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The effect of chronic ethanol consumption on cerebral cortical activity of Na,K-ATPase was determined in Long-Evans (LE) rats fed an ethanol-containing diet beginning at different stages of development. Na,K-ATPase activity was operationally resolved into α1 and α2/3 isozyme activities. There was no significant difference in Na,K-ATPase activities before and after alcohol consumption in the preparations from adult rats. However, for rats beginning alcohol consumption as adolescents, the α2/3 activity was significantly elevated following chronic alcohol consumption. Both LE and Sprague–Dawley rats showed this same selective increase in cortical α2/3 activity when rats began alcohol consumption as juveniles. The shift in cortical α2/3 activity was not observed in cerebellum or subcortical forebrain and was reversible when rats were fed ethanol throughout the normal adolescent period and then withdrawn and tested 2 weeks later (during the adult period). Levels of isoform-specific mRNA were determined in preparations of cerebral cortices of rats showing elevated α2/3 isozyme activities. In these preparations, isoform specific α2 and α3 mRNA was significantly elevated. There was no effect of ethanol feeding on cortical α1 mRNA. These findings indicate that the longer term effects of ethanol on the developing brain include elevated Na,K-ATPase activity and a mechanism that is pre-translational and isoform specific.
KeywordsAdolescence Brain development Chronic ethanol consumption mRNA levels Na K-ATPase Long-Evans rat
Early portions of this work were supported by PHS grant AA07848 and by a grant-in-aid from the URI Council for Research. The authors thanks Dr. Jerry B. Lingrel for providing the isozyme specific probes, Dr. Joel Chandlee for providing lab space and advice on Northern blot analysis, Dr. Paul Cohen for providing E. coli HB101, Dr. Stanley Bower for providing M13/pUC primers, and Dr. Brian Maynard for advice and use of the NIH image analysis program for slot blot analysis. The authors acknowledge the assistance of Ms. Jane Knapp and Dr. Jiongdong Pang with the Northern blot analysis and the help of Sean Casavant, Philip Empey, Joe Susa, and Bruno Soffientino (URI) in administering the liquid diets and caring for the animals. Jennifer Huggan (MU) assisted in BAC determinations.
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