CORE--NEUROCHEMISTRY

核心--神经化学

• 批准号: 7457813
• 负责人: Holly Marie Moore
• 金额: $ 18.17万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7457813
• 关键词: Affinity; Amino Acids; Amphetamines; Animal Model; Binding; Biological Assay; Brain; Brain imaging; Catecholamines; Development; Dopamine; Drug Kinetics; Experimental Designs; Glutamates; Human; Human Resources; Image; In Vitro; Investigation; Laboratories; MK801; Methods; Microdialysis; Mission; Molecular; Mus; NNC 112; Neurotransmitters; Plasma; Primates; Risperidone; Rodent; Sampling; Screening procedure; Synapses; Technical Expertise; Techniques; Work; brain tissue; extracellular; in vivo; indolamine; indoleamine; method development; model development; neurochemistry; nonhuman primate; novel; radioligand; radiotracer; receptor; receptor binding; trafficking

The Neurochemistry Core will integrate and consolidate the activities performed in several basic laboratories of this Center into three units, under the direction of Drs Moore, Cooper and Javitch, respectively: 1) In vivo and ex vivo determination of brain catecholamine, indoleamine and amino acid transmitter levels (Moore). This unit will provide logistical support and technical expertise to projects of the Center that employ in vivo microdialysis in rodents and primates (Projects by Laurelle, Kandel, Rayport) including experimental design, implementation, and chromatographic analysis of catecholamines, indolamines and amino acids in in vivo brain dialysate samples and ex vivo brain tissue homogenates (Projects by Laurelle, Javitt, Kandel, Rayport). 2) Pharmacokinetic Unit (Cooper). This unit will develop and perform analysis of plasma levels of pharmacological agents (e.g. MK 801, NNC 112, SCH 39166, amphetamine, PCP, risperidone) used in mice (Projects by Kandel, Rayport ); non-human primates (Projects by Laurelle and Project by Javitt) and humans (Projects by Abi-Dargham and Laurelle). 3) Receptor Binding Unit (Javitch). This unit will integrate activiiies performed in the laboratories of Javitch, Rayport, and Huang. The first mission is to perform in vitro binding assay and to characterize candidate radioligands developed by the Brain Imaging Core and Projects by Abi-Dargham and Project by Laurelle. The second mission is to study the impact of receptor trafficking on binding affinities of D2 and D1 radiotracers. The latter investigation will provide important information for imaging studies using endogenous competition techniques such as used in Project by Laurelle, and will contribute to the development of novel radioligands with binding that is sensitive to changes in synaptic/extracellular concentrations of endogenous transmitters, specifically dopamine and glutamate (see Brain Imaging Core). In summary, the Neurochemistry Core will share personnel and will work closely with Projects by Abi-Dargham, Laurelle, Javitt, Kandel & Rayport and the Brain Imaging Core and Cellular/Molecular Core to provide screening and hypothesis-directed characterization of neurotransmitter profiles in animal models, development of novel methods for combining in vivo microdialysis and functional brain imaging in primates and rodents, and development of methods for characterization of candidate radioligands for functional brain imaging.

神经化学核心将整合和巩固在几个基本的活动中进行的活动 在摩尔博士，库珀和贾维奇的指导下，该中心的实验室分为三个单位 分别： 1）体内和离体测定脑儿茶酚胺，吲哚美胺和氨基酸 发射机水平（摩尔）。该单元将为在啮齿动物和灵长类动物中采用体内微透析的中心项目（Laurelle，Laurelle，Kandel，Rayport的项目）提供后勤支持和技术专业知识体内脑透析样品和离体脑组织匀浆（Laurelle，Javitt，Kandel，Rayport的项目）。 2）药代动力学单位（库珀）。该单元将开发和执行血浆水平的分析 用于小鼠的药理学剂（例如MK 801，NNC 112，SCH 39166，Amphetamine，PCP，Risperidone）（Kandel，Rayport的项目）；非人类灵长类动物（Laurelle和Javitt的项目）和人类（Abi-Dargham和Laurelle的项目）。 3）受体结合单元（Javitch）。该单元将整合实验室中执行的活动 Javitch，Rayport和Huang的作品。第一个任务是执行体外结合测定法，并表征由Abi-Dargham和Laurelle的Project开发的候选放射线。 第二个任务是研究受体运输对D2和D1辐射示例的结合亲和力的影响。后者的研究将使用内源性竞争技术（例如Laurelle在Project中使用）为成像研究提供重要信息，并将有助于与新型放射线的发展 对内源性发射器（特别是多巴胺和谷氨酸）突触/细胞外浓度变化敏感的结合（请参阅脑成像核心）。 总而言之，神经化学核心将共享人员，并将与Abi-Dargham，Laurelle，Javitt，Kandel和Rayport以及大脑成像核心和蜂窝/分子核心的项目紧密合作，以提供筛查和假设指导的动物神经递谱表征模型，开发用于在灵长类动物和啮齿动物中结合体内微透析和功能性脑成像的新方法，以及用于表征候选放射性射线体进行功能性脑成像的方法的开发。