The overall goal of this project is to identify genes which are differentially expressed in alcoholics as compared to non-alcoholics. This will be accomplished by collecting autopsy material from individuals extensively characterized for drinking history, other pathologies, drug and tobacco use, brain histology, and genotype. In addition to the existing Australian Brain Bank, one of the most extensive for alcoholic cases available in the world, emphasis will be placed on collecting additional cases with specific attributes, such as abstinent alcoholics. Gene expression will be measured in frontal and motor cortex by microarrays that simultaneously measure levels of up 7000 expressed genes from a single sample of brain RNA. Our preliminary results demonstrate the feasibility of these approaches and suggest changes in gene expression consistent with published studies as well as changes in novel genes. About 30 genes of particular merit and interest will be selected for detailed analysis with a particular emphasis on correlating changes in mRNA expression to protein expression. Gene expression in the alcoholic brain may be changed due to predisposing factors (susceptibility genes), as a consequence of chronic ethanol exposure (alcohol responsive genes) or as a consequence of alcoholic neuropathology, other pathology (e.g., cirrhosis) or co-morbidity (e.g., tobacco use). We propose that careful case selection for analysis of gene expression will allow us to distinguish among (at least some of) these possibilities.
| Mayfield, R Dayne; Harris, R Adron (2018) Persistence of Drug Memories: Melting Transcriptomes. Biol Psychiatry 84:860-861 |
| Erickson, Emma K; Farris, Sean P; Blednov, Yuri A et al. (2018) Astrocyte-specific transcriptome responses to chronic ethanol consumption. Pharmacogenomics J 18:578-589 |
| Most, Dana; Salem, Nihal A; Tiwari, Gayatri R et al. (2018) Silencing synaptic MicroRNA-411 reduces voluntary alcohol consumption in mice. Addict Biol : |
| Ferguson, Laura B; Ozburn, Angela R; Ponomarev, Igor et al. (2018) Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice. Neuropsychopharmacology 43:1257-1266 |
| McCarthy, Gizelle M; Warden, Anna S; Bridges, Courtney R et al. (2018) Chronic ethanol consumption: role of TLR3/TRIF-dependent signaling. Addict Biol 23:889-903 |
| Osterndorff-Kahanek, Elizabeth A; Tiwari, Gayatri R; Lopez, Marcelo F et al. (2018) Long-term ethanol exposure: Temporal pattern of microRNA expression and associated mRNA gene networks in mouse brain. PLoS One 13:e0190841 |
| McCarthy, Gizelle M; Farris, Sean P; Blednov, Yuri A et al. (2018) Microglial-specific transcriptome changes following chronic alcohol consumption. Neuropharmacology 128:416-424 |
| Mayfield, R Dayne (2017) Emerging roles for ncRNAs in alcohol use disorders. Alcohol 60:31-39 |
| Mayfield, Jody; Harris, R Adron (2017) The Neuroimmune Basis of Excessive Alcohol Consumption. Neuropsychopharmacology 42:376 |
| Harris, R Adron; Bajo, Michal; Bell, Richard L et al. (2017) Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents. J Neurosci 37:1139-1155 |
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