Differentially Expressed Genes in the Nucleus Accumbens from Chronically Ethanol-Administered Rat.

Abstract

The isolation of differentially expressed genes in the nucleus accumbens (NA) from chronically ethanol-administered rats may help in understanding the underlying molecular mechanisms for the development and reinforcement of ethanol addiction. The differential display indicated that around 0.1‐0.2% of mRNA could be considered to be affected by chronic ethanol-administration in the NA, regardless of whether ethanol directly affected gene expression in the NA or the gene alteration was secondary to changes in neuronal activity caused by ethanol. Forty-six clones were successfully reamplified, and screening by reverse Northern blot analysis resulted in the isolation of five up-regulated and three down-regulated genes. One of the up-regulated cDNAs was homologous to human TGFβ1 and its preferential expression was also observed in the cerebellum and locus coeruleus (LC). Since clone c10 displayed an extremely strong preferential expression in the ethanol-administered NA, its upstream sequence was analyzed by 5′ rapid amplification of DNA ends (5′RACE) but the coding sequence has not yet been isolated. c118 showed enrichment in the ethanol-administered NA and displayed strong homology to the mouse KH domain RNA binding protein QKI-5A. The 5′RACE analysis confirmed that this clone encoded rat QKI-5A. Since QKI proteins are considered to be regulators of myelination and their absence causes dysmyelination, its up-regulation may offer protection against ethanol-induced dysmyelination. Another 12 cDNAs were registered as expression sequence tags (ESTs) or novel with their functions unknown. It is considered important, however, that to their upstream sequences including coding regions and promoter sequences are identified not only to estimate the roles of these differentially expressed genes in ethanol addiction but also to clarify whether ethanol-dependent gene-regulation can occur or not.