We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Neurotoxic Consequences of Chronic Alcohol Withdrawal: Expression Profiling Reveals Importance of Gender Over Withdrawal Severity.
- Authors
Hashimoto, Joel G.; Wiren, Kristine M.
- Abstract
While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways were more altered by alcohol. Examination of ethanol-regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse.Neuropsychopharmacology (2008) 33, 1084–1096; doi:10.1038/sj.npp.1301494; published online 27 June 2007
- Subjects
NEUROTOXICOLOGY; DRUG withdrawal symptoms; ALCOHOL withdrawal syndrome; BRAIN damage; ALCOHOLISM; ALCOHOL &; sex
- Publication
Neuropsychopharmacology, 2008, Vol 33, Issue 6, p1084
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/sj.npp.1301494