The effects of chronic ethanol abuse on the brain and body can have a devastating impact on health and well-being, and predispose individuals toward risky behaviors that might even result in premature death. In order to reduce the prevalence of alcohol abuse, we need to improve our ability to detect the earliest signs of damage to the central or internal organs, which might enable appropriate interventional or therapeutic strategies to be initiated. The goal of this project is to develop screening tools that could have true translational potential for diagnosing when the earliest signs, of ethanol-induced damage to the brain has occurred. This information will be acquired through a careful series of experiments involving laboratory rats that are engaged in drinking behaviors for variable periods of time, beginning either as adults or adolescents, and are determined to have signs of central or internal organ damage. The peripheral blood of these animals will be monitored for signs of liver or heart damage in order to guard against the possibility that the effects we observe in the blood are not specific for the brain. ? ? Total RNA will be extracted from the circulating leukocytes to determine those genes with expression patterns that are significantly correlated (both positively and negatively) with RNA levels in three different brain regions (cerebellum, hippocampus, and somatosensory cortex) of the same animal. In the same animals, we will also assess potential liver or cardiac damage by monitoring serum ALT and AST levels. We will use the expression information as background data for a second phase of investigation, involving the collection of peripheral blood and screening of RNA from human subjects who are currently undergoing treatment for alcohol abuse who are positive or negative for signs of CNS, liver, or heart damage. In the end, we hope to identify a small subset of genes with diagnostic and prognostic utility that could be used to identify at risk individuals in order to commence treatment and tailor this treatment toward their specific pattern of alterations. ? ? ?
| Hicks, Steven D; Lewis, Lambert; Ritchie, Julie et al. (2012) Evaluation of cell proliferation, apoptosis, and DNA-repair genes as potential biomarkers for ethanol-induced CNS alterations. BMC Neurosci 13:128 |
| Meszaros, Zsuzsa Szombathyne; Dimmock, Jacqueline A; Ploutz-Snyder, Robert et al. (2011) Accuracy of self-reported medical problems in patients with alcohol dependence and co-occurring schizophrenia or schizoaffective disorder. Schizophr Res 132:190-3 |
| Hicks, Steven D; Middleton, Frank A; Miller, Michael W (2010) Ethanol-induced methylation of cell cycle genes in neural stem cells. J Neurochem 114:1767-80 |
