Ethanol-regulated gene expression of neuroendocrine specific protein in mice: brain region and genotype specificity

Neuroendocrine specific protein or reticulon 1 (NSP/RTN1) was identified as a putative ethanol-regulated gene using mRNA differential display in mice genetically selected for severe ethanol withdrawal (withdrawal seizure-pron e, WSP). One transcript of RTN1 (3.0 kb) showed a statistically significant increase (13%) in relative abundance in whole brain of ethanol-treated WSP mice but not in mice selected for resistance to ethanol withdrawal convuls ions (WSR). We hypothesized that ethanol-induced regulation of gene express ion of mRTN1 is specific to mice predisposed to exhibit severe ethanol with drawal and that the gene might be regulated differentially in specific brai n regions. WSP and WSR selected lines and DBA/2J and C57BL/6J inbred strain s of mice were exposed to ethanol vapor or air for 72 h. mRNA steady-state expression of RTN1 was assessed in hippocampus, cortex, and cerebellum. Res ults indicated that the pattern of ethanol-induced changes in gene expressi on was dependent upon transcript size, brain region, and genotype. Modest i ncreases in the relative abundance of both transcripts of RTN1 were observe d in the hippocampus and cortex of all ethanol-treated mice. Results from c erebellum showed a moderate decrease in expression of RTN1 (3.0 kb transcri pt) in WSP and DBA/2J mice, but not in the mice resistant to ethanol withdr awal (C57BL/6J and WSR). These results suggest a genotype-specific effect o f chronic ethanol exposure on steady-state mRNA levels of RTN1 in the cereb ellum. Overall, the results indicate a complex pattern of ethanol-induced r egulation of the putative mouse homologue of RTN1 and suggest that specific brain regional changes may be involved in the expression of physical depen dence. (C) 2001 Elsevier Science B.V. All rights reserved.