Alcoholism is associated with several neurological diseases accompanied by aberrant myelination. Functional genomics techniques, which can provide simultaneous, non-biased measurement of expression levels for thousands of genes, have been applied to problems of alcohol-related neurological disease. DNA microarray studies demonstrate coordinate decrease of myelin-related genes in frontal cortex of human alcoholics. We have observed a coordinate increase in expression of myelin-related genes in prefrontal cortex of adult DBN2J mice in response to acute ethanol. This effect was blocked by naltrexone. Together, these data suggest that acute and chronic ethanol differentially regulate myelin gene expression. We hypothesize that a crucial signaling pathway, which may involve opioid receptor and/or cAMP signaling, is responsible for regulation of myelin by ethanol. The goal of this application is to characterize this mechanism by fulfilling the following specific areas: 1) Characterize myelin gene expression with specific opioid receptor antagonists in control and ethanol-treated DBA mice. 2) Characterize myelin gene expression in control and ethanol-treated mature cultured mouse oligodendrocytes. 3) Confirm the role of transfected candidate genes in mature oligodendrocyte cell culture. These studies into myelin regulation by ethanol may give novel insight into signaling events evoked by acute ethanol and the mechanism(s) of certain of alcohol-associated neurological disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AA014726-01A1
Application #
6837964
Study Section
Special Emphasis Panel (ZAA1-EE (10))
Program Officer
Guo, Qingbin
Project Start
2004-09-16
Project End
2006-09-15
Budget Start
2004-09-16
Budget End
2005-09-15
Support Year
1
Fiscal Year
2004
Total Cost
$55,708
Indirect Cost
Name
Virginia Commonwealth University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
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Goldowitz, Daniel; Matthews, Douglas B; Hamre, Kristin M et al. (2006) Progress in using mouse inbred strains, consomics, and mutants to identify genes related to stress, anxiety, and alcohol phenotypes. Alcohol Clin Exp Res 30:1066-78