Pathophysiogenomic markers:ethanol-induced brain damage

描述（由申请人提供）：长期滥用乙醇对大脑和身体的影响会对健康和福祉产生毁灭性的影响，并使个人倾向于危险的行为，甚至可能导致过早死亡。为了减少酒精滥用的流行，我们需要提高我们发现中枢或内部器官受损的最早迹象的能力，这可能使适当的介入或治疗策略得以启动。这个项目的目标是开发一种筛查工具，当酒精引起的大脑损伤出现早期迹象时，这种工具可能具有真正的转化潜力，用于诊断。这一信息将通过一系列仔细的实验获得，这些实验涉及实验室老鼠，这些老鼠从成年或青少年开始，在不同时期有饮酒行为，并被确定有中枢或内部器官损伤的迹象。我们将对这些动物的外周血进行监测，以寻找肝脏或心脏受损的迹象，以防止我们在血液中观察到的影响并非针对大脑的可能性。

DESCRIPTION (provided by applicant): 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.