PROGRAM IN MOLECULAR NEUROBIOLOGY & DEVELOPMENTAL DISORD

分子神经生物学项目

• 批准号: 3075603
• 负责人: ROLAND D CIARANELLO
• 金额: $ 10.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3075603
• 关键词: G protein; adolescence (12-20); antidepressants; beta adrenergic receptor; binding proteins; brain; child (0-11); child mental disorders; clinical depression; early infantile autism; genetic library; genetic manipulation; genetic markers; human population genetics; laboratory rat; linkage mapping; messenger RNA; molecular cloning; molecular pathology; neurobiology; neurotransmitters; polymerase chain reaction; psychological tests; questionnaires; receptor expression; renal medulla; serotonin; serotonin receptor

This is a revised application for an ADAMHA Research Scientist Award. It describes in part my work as principal investigator and program director for the research program in Molecular Neurobiology and Developmental Disorders. The program consists of an administrative and scientific core serving five major investigative areas. Each area has as its central theme the application of molecular neurobiology to an understanding of developmental processes and their regulation. Studies in the Regulation of Serotonin and beta-adrenergic Receptors section (Roland D. Ciaranello, M.D., Project Director) examine the regulation of serotonin and beta- adrenergic receptor mRNA and G-protein coupling during development, as well as the regulation of these receptor mRNAs by antidepressants and drugs which alter neurotransmission. The work seeks to understand those factors which initiate and maintain receptor gene expression. The section on Enzyme Regulation (Dona L. Wong, Ph.D., Project Director) focuses on hormonal and neuronal regulation of phenylethanolamine N-methyltransferase (PNMT) gene expression during development. These studies examine differences in prenatal and postnatal mechanisms regulating enzyme expression. The section on Developmental Neurobiology of Canine Narcolepsy (William C. Dement, M.D., Ph.D., Project Director) uses an animal model of narcolepsy, an autosomal recessive disorder which afflicts young adolescents and children, to examine defects in cholinergic and alpha-1-adrenergic receptors. The research strategy utilizes the differential maturation of the relevant neurotransmitter systems to help localize the specific neurochemical lesion(s). in the section on Characterization of Developmentally Regulated Genes (John L.R. Rubenstein, M.D., Ph.D., and Roland D. Ciaranello, M.D, Project Codirectors), we are devising methods of isolating and characterizing genes which are expressed during discrete developmental epoches. We hope to identify those genes which regulate the architectural development of the cerebral cortex. Finally, the section on Molecular and Linkage Genetics of Infantile Autism (Project F, Luigi Cavalli-Sforza, M.D., Project Director) describes work seeking to find a gene marker for infantile autism in multiple-incidence families. This Research Scientist Award application describes in detail my work in the sections on receptor regulation and autism genetics.

这是一份修改后的ADAMHA研究科学家奖申请表。它 描述了我作为首席研究员和项目主任的部分工作 分子神经生物学和发育研究项目 精神失常。该计划由行政和科学核心组成 服务于五大调查领域每个区域都有其中心主题 应用分子神经生物学来理解 发展过程及其调控。研究的规管 血清素和β-肾上腺素能受体部分（罗兰D.恰拉内洛， 医学博士，项目主任）检查血清素和β-羟色胺的调节， 肾上腺素能受体mRNA和G蛋白偶联在发育过程中，以及 抗抑郁药和药物对这些受体mRNA的调节 从而改变神经传递这项工作试图了解这些因素 启动和维持受体基因表达。关于酶的部分 监管（Dona L. Wong博士，项目总监）专注于荷尔蒙和 苯乙醇胺N-甲基转移酶基因的神经调节 发展过程中的表达。这些研究考察了 调节酶表达的产前和产后机制。该科 关于犬嗜睡症的发育神经生物学（William C.德门特， 医学博士，哲学博士、项目主任）使用嗜睡症的动物模型， 常染色体隐性遗传疾病折磨年轻的青少年和儿童， 检查胆碱能和α 1肾上腺素能受体的缺陷。的 研究策略利用相关的差异成熟 神经递质系统帮助定位特定的神经化学物质 病变。在发育受调节的 基因（John L.R.鲁宾斯坦医学博士，哲学博士、和罗兰D. Ciaranello，医学博士， 项目共同主任），我们正在设计隔离和 表征在离散发育过程中表达的基因 时代我们希望能够识别出那些调控细胞结构的基因， 大脑皮层的发育。最后，关于分子和 婴儿自闭症的连锁遗传学（项目F，Luigi Cavalli-Sforza， 医学博士，项目主任）描述了寻找基因标记的工作， 多发病家庭中的婴儿自闭症。本研究科学家 获奖申请详细介绍了我的工作在受体部分 调节和自闭症遗传学。