RECEPTOR MRNA ANALYSIS OF HUMAN BRAIN TISSUES

酒精中毒时发生的神经递质紊乱， 慢性酒精使用还不太清楚。 尽管各种 神经适应机制已经从以下模型实验中推断出来： 动物，这些机制与人类酒精中毒的相关性并不重要。 很好的。 一种检验神经递质假说的方法 干扰是评估参与基因的表达， 神经传递在死后标本的特定区域的 人脑mRNA原位杂交。 这项技术具有 提供关于表达的非常具体的信息的优点 动物和临床研究所针对的特定基因， 受酒精中毒影响。 然而，该技术还要求， 死后标本中的mRNA不被非特异性 因素，包括酗酒本身造成的衰弱。 本研究的第一个目的是获得死后脑组织， 40名酗酒者和40名正常人，并分析mRNA含量， 完整 将对数据进行分析，以确定非特异性 与酒精使用或死亡相关的因素， 尸检，影响mRNA的含量和完整性。 第二个目标是 检查GABA-A受体相关基因的表达，包括 γ-2-L成分，它传递对酒精的敏感性。 第三 目的是检测β肾上腺素能受体的表达， 也与对酒精的反应有关 因此，该组件将 支持人类神经生物学和分子生物学的研究 生物学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.