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进行 该中心的实验室分为三个单位，在博士摩尔，库珀和Javitch的指导下， 分别为： 1)脑组织中儿茶酚胺、吲哚胺和氨基酸的体内外测定 发射机电平（摩尔）。该单位将为该中心的啮齿动物和灵长类动物体内微透析项目（Laurelle、Kandel、Rayport项目）提供后勤支持和技术专长，包括体内脑透析液样品和离体脑组织匀浆中儿茶酚胺、吲哚胺和氨基酸的实验设计、实施和色谱分析（Laurelle、Javitt、Kandel、Rayport项目）。 2)药代动力学单位（库珀）。该单位将开发和执行血浆水平的分析， 用于小鼠（Kandel，Rayport的项目）、非人灵长类动物（Laurelle的项目和Javitt的项目）和人（Abi-Dargham和Laurelle的项目）的药理学试剂（例如MK 801、NNC 112、SCH 39166、安非他明、PCP、利培酮）。 3)受体结合单位（Javitch）。该单位将整合实验室开展的活动 贾维奇雷波特和黄第一个使命是进行体外结合试验，并表征由Abi-Dargham的脑成像核心和项目以及Laurelle的项目开发的候选放射性配体。 第二个使命是研究受体运输对D2和D1放射性示踪剂结合亲和力的影响。后一项研究将为使用内源性竞争技术（如Laurelle的Project中使用的技术）的成像研究提供重要信息，并将有助于开发具有以下功能的新型放射性配体： 结合，对内源性递质的突触/细胞外浓度的变化敏感，特别是多巴胺和谷氨酸（见脑成像核心）。 总之，神经化学核心将共享人员，并将与Abi-Dargham，Laurelle，Javitt，Kandel & Rayport以及脑成像核心和细胞/分子核心的项目密切合作，以提供动物模型中神经递质谱的筛选和假设指导表征，开发用于结合灵长类动物和啮齿动物体内微透析和功能性脑成像的新方法，以及开发用于表征用于功能性脑成像的候选放射性配体的方法。