RECEPTOR MRNA ANALYSIS OF HUMAN BRAIN TISSUES

人脑组织受体 mRNA 分析

• 批准号: 3745278
• 负责人: ROBERT FREEDMAN
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745278
• 关键词: GABA receptor; alcoholism /alcohol abuse; behavioral genetics; beta adrenergic receptor; cerebellum; cryopreservation; ethanol; frontal lobe /cortex; gene expression; hippocampus; human genetic material tag; human tissue; in situ hybridization; messenger RNA; neural transmission; neuropharmacology; northern blottings; pharmacogenetics; postmortem; receptor expression; tissue /organ preservation; tissue resource /registry

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.

酗酒期间发生的神经递质干扰 慢性饮酒尚不清楚。 虽然多种 从模型实验中推断出神经适应机制 动物，这些机制与人类酒精中毒的相关性不是 建立的。 一种检验神经递质假设的方法 干扰是评估涉及的基因的表达 神经传递在特定区域的验尸标本中 人脑通过原位杂交mRNA。 该技术具有 提供有关表达的非常具体信息的优势 动物和临床研究针对的特定基因 受酒精中毒的影响。 但是，该技术还要求 验尸标本中的mRNA不会被非特异性降解 因素，包括酗酒本身造成的衰弱。 这项研究的第一个目的是从 40种酒精和40个正常，并分析mRNA含量和 正直。 将分析数据以确定是否非特异性 因素，与饮酒有关或与死亡事件有关的因素和 尸检，影响mRNA含量和完整性。 第二个目标是 检查与GABA-A受体有关的基因的表达，包括 γ-2-L成分，传达对酒精的敏感性。 第三 目的是检查具有β肾上腺素能受体的表达 也与对酒精的反应有关。 因此，此组件将 对神经生物学和分子的人类的支持调查 也是动物研究重点的生物学机制 其他中心项目中的模型。