RGS Protein (2,4,9,10) Survey in Schizophrenia

精神分裂症中的 RGS 蛋白 (2,4,9,10) 调查

• 批准号: 6725242
• 负责人: Michael W Vogel
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725242
• 关键词: basal ganglia; biological signal transduction; cingulate gyrus; clinical research; dopamine; frontal lobe /cortex; human tissue; immunocytochemistry; in situ hybridization; neurochemistry; postmortem; protein localization; protein quantitation /detection; protein structure function; schizophrenia

DESCRIPTION (provided by applicant): RGS (Regulators-of-G-Protein-Signaling) proteins are a family of substances functionally related to G protein receptors and are located intracellularly near receptors. They function to terminate the action of agonist stimulation at a linked G protein-coupled receptor. These proteins have been described largely in animal brain and have not yet been fully characterized in human tissue. Evidence of their relevance to human brain diseases, especially to schizophrenia, is scant. Because schizophrenia is an illness responsive to dopamine receptor blockade, and possibly associated with augmented dopamine release, all parts of the dopamine system which participate in dopaminergic signal transduction deserve examination for potential association with pathophysiology. Moreover, RGS-4 (one of over 20 RGS proteins) has already been implicated in schizophrenia by microarray data and in situ hybridization in frontal cortex from one (but not from all) laboratories doing unbiased expression analysis in schizophrenia. Thus, based on a rational hypothesis and based on one piece of experimental data, relevant RGS proteins deserve a comprehensive survey in schizophrenia. If, after this analysis, we identify a signal in the schizophrenia cases, of abnormal quantities or distribution of any of these four RGS proteins, we will gear-up for a full characterization of the functional defect in the illness. We request funding in this small grant application for an initial screen of the four RGS proteins most closely related to dopamine, their regional densities in the normal and schizophrenia tissue and any differences from normal in either protein levels (by immunohistochemistry) or in protein expression (by in situ hybridization and Western analysis. Because of our previous work in schizophrenia neurochemistry, we have existing tissue blocks from schizophrenia (on treatment drugs), schizophrenia (off-drug x 6 mo), and matched control cases to use for this analysis. Thus, we can accomplish this experiment in a timely manner.

描述（由申请人提供）：RGS（G蛋白信号调节剂）蛋白是一个与G蛋白受体功能相关的物质家族，位于细胞内受体附近。它们的作用是终止激动剂对连接的G蛋白偶联受体的刺激作用。这些蛋白质主要在动物脑中描述，但尚未在人体组织中完全表征。它们与人类大脑疾病，特别是精神分裂症有关的证据很少。因为精神分裂症是一种对多巴胺受体阻断有反应的疾病，并且可能与多巴胺释放增加有关，所以参与多巴胺能信号转导的多巴胺系统的所有部分都值得检查与病理生理学的潜在关联。此外，RGS-4（超过20种RGS蛋白之一）已经通过来自一个（但不是所有）实验室的额叶皮质中的微阵列数据和原位杂交在精神分裂症中进行无偏表达分析而与精神分裂症有关。因此，基于一个合理的假设和一个实验数据的基础上，相关的RGS蛋白值得在精神分裂症中进行全面的调查。如果在分析之后，我们在精神分裂症病例中发现了这四种RGS蛋白中任何一种的异常数量或分布的信号，我们将准备对疾病中的功能缺陷进行全面表征。我们要求在这个小的赠款申请的资金，用于四个RGS蛋白质的最密切相关的多巴胺，其区域密度在正常和精神分裂症组织和任何差异，从正常的蛋白质水平（通过免疫组化）或蛋白质表达（通过原位杂交和Western分析的初始屏幕。由于我们之前在精神分裂症神经化学方面的工作，我们有来自精神分裂症（治疗药物）、精神分裂症（停药x 6个月）和匹配对照病例的现有组织块用于本分析。因此，我们可以及时完成这项实验。