ALCOHOL EFFECTS ON BRAIN PROTEIN EXPRESSION PROFILES

DESCRIPTION (provided by applicant): A large body of evidence indicates that genetic factors play a major role in influencing alcohol-drinking behavior in humans and animals. A central goal in alcohol research is to find exploitable differences between alcohol preferring and non-preferring humans or animals. Exploitable protein differences may involve post-translational modifications or expression changes that result from a complex series of events not easily discernable at the DNA or mRNA level. Hence it is important to attempt to explore differences at both the genomic and proteomic levels, in as systematic a manner as possible. Using advanced proteomics technologies, we propose a project to study protein expression patterns in the brains of rats which are 1) bred for either high or low alcohol consumption and 2) exposed to alcohol or saline for five days. The applied and combined technologies include rat line breeding, brain tissue dissection, quantitative high resolution two-dimensional electrophoresis (2DE), mass spectrometry and data mining. Comparing innate differences in protein expression in the brains of these lines following treatment with alcohol should give insight on protein factors that may contribute to vulnerability to alcohol addiction and proteins affected by alcohol. Furthermore, providing a comprehensive database for regional protein expression in the brains of the selectively bred rats and the effect of alcohol on individual brain regions would lay an important foundation for other basic and clinical researchers in the field of alcohol abuse and alcoholism. The ultimate objective is to discover biomarkers which will have a great impact on early diagnosis and improved monitoring and treatment of alcohol-related diseases.