RECEPTOR MRNA ANALYSIS OF HUMAN BRAIN TISSUES

酗酒和酗酒期间发生的神经递质紊乱 长期饮酒尚不十分清楚。 虽然各有不同 神经适应性机制已从模型实验中推断出来 在动物中，这些机制与人类酗酒的相关性并不 完善的。 检验神经递质假设的一种方法 干扰是为了评估参与的基因的表达 特定区域死后标本中的神经传递 通过 mRNA 原位杂交检测人脑。 该技术具有 提供有关表达的非常具体的信息的优点 动物和临床研究已针对的特定基因 受到酗酒的影响。 然而，该技术还要求 死后标本中的 mRNA 不会被非特异性降解 因素，包括酗酒本身造成的虚弱。 本研究的首要目的是获取死后脑组织 40 名酗酒者和 40 名正常人并分析 mRNA 含量和 诚信。 将分析数据以确定是否非特定 与饮酒或与死亡相关的事件有关的因素，以及 尸检，影响 mRNA 含量和完整性。 第二个目标是 检查与 GABA-A 受体相关的基因的表达，包括 γ-2-L 成分，表达对酒精的敏感性。 第三个 目的是检查β肾上腺素能受体的表达，该受体具有 也与酒精反应有关。 因此，该组件将 支持人类神经生物学和分子学研究 生物机制也是动物研究的重点 其他中心项目中的模型。

The neurotransmitter disturbances which occur during alcoholism and chronic alcohol use are not well understood. Although various neuroadaptive mechanisms have been inferred from model experiments in animals, the relevance of these mechanisms to human alcoholism is not well-established. One method to test hypotheses of neurotransmitter disturbance is to assess the expression of genes involved in neurotransmission in post mortem specimens of specific regions of the human brain by in situ hybridization of mRNA. This technique has the advantage of providing very specific information about the expression of specific genes which animal and clinical research have targeted as affected in alcoholism. However, the technique also requires that the mRNA in the post mortem specimens not be degraded by non-specific factors, including the debilitation produced by alcohol abuse itself. The first aim of this study is to obtain post mortem brain tissue from 40 alcoholics and 40 normals and to analyze the mRNA content and integrity. The data will be analyzed to determine if non-specific factors, related to alcohol use or to the events surrounding death and autopsy, influence mRNA content and integrity. The second aim is to examine the expression of genes related to GABA-A receptors, including the gamma-2-L component, which conveys sensitivity to alcohol. The third aim is to examine the expression of beta adrenergic receptors, which have also been linked to the response to alcohol. This component will thus support investigations in humans of neurobiological and molecular biological mechanisms that are also the focus of research in animal models in other Center projects.