CORE--BRAIN IMAGING

核心--脑成像

• 批准号: 7248773
• 负责人: MARK SLIFSTEIN
• 金额: $ 15.83万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 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/7248773
• 关键词: AMPA receptors; NMDA receptors; baboons; bioimaging /biomedical imaging; biomedical facility; brain imaging /visualization /scanning; chemical synthesis; dopamine; glutamates; laboratory mouse; laboratory rat; magnetic resonance imaging; method development; neural transmission; neurochemistry; neurotransmitter agonist; positron emission tomography; radiotracer; schizophrenia

Numerous lines of evidence reviewed in the introduction of this CCNMD sugges(that alterations of dopamine (DA) neurotransmission are associated with schizophrenia. Recent development of methods to assess DA neurotransmission in vivo with PET allows direct testing of this hypothesis in patients. The Brain Imaging Core is an integrated team of scientists from various disciplines (chemistry, pharmacology, physics, mathematics), covering the range of expertise needed to develop and support PET neuroreceptor and mouse MRI studies. The services provided to the Center by the Brain Imaging Core fall into three general categories: 1) To provide logistical support and technical expertise to brain imaging projects of the Center. The Core provides expertise at the level of study design, implementation, and analysis. In addition, these studies benefit from the general infrastructure maintained by the Core, such as radiochemistry and image analysis laboratories. 2) To provide training in brain imaging to young investigators. These include young psychiatrists, who are completing a fellowship in the Division of Functional Brain Mapphng as Well as other investigators in the Center who are interested in applying brain imaging techniques to the study of schizophrenia. 3) To develop new imaging modalities that are pertinent to schizophrenia research. Over the next five years, our efforts will be targeted at examining the DA and glutamate systems with PET. We will focus on the following objectives, guided by a general model of neurochemical imbalance associated with schizophrenia described in the Introduction to the Center. a) To continue the characterization of the in vivo properties of the D2 agonist we have radiolabeled; b) To develop a new D1 receptor radiotracer whose binding is affected by acute fluctuations in endogenous DA; c) To develop a radiotracer that labels the NR2B site of the NMDA methods we have applied in other settings to the mouse models of schizophrenia explored in several of the Projects, and f) to continue to refine the voxelwise kinetic modeling methods we have developed. Together, these projects should provide new and sophisticated tools for the study of schizophrenia. The radiotracers and methods developed during this funding cycle of the Center will be made available to the scientific community.

在引入该CCNMD建议时审查了许多证据（多巴胺（DA）神经传递的改变与精神分裂症有关。最近开发了用PET评估DA神经传递的方法，可以直接在患者中对此假设进行直接检验。大脑成像。 Core是来自各种学科的科学家团队（化学，药理学，物理，数学），涵盖了开发和支持PET神经受体和鼠标MRI研究所需的专业知识范围。三个一般类别： 1）为中心的大脑成像项目提供后勤支持和技术专长。核心在研究设计，实施和分析的水平上提供了专业知识。此外，这些研究受益于核心维护的一般基础设施，例如放射化学和图像分析实验室。 2）向年轻研究人员提供脑成像的培训。其中包括年轻的精神科医生，他们正在完成功能性脑部Mapphng的奖学金以及中心的其他研究人员，他们有兴趣将脑成像技术应用于精神分裂症的研究。 3）开发与精神分裂症研究有关的新成像方式。在接下来的五年中，我们的努力将针对使用PET检查DA和谷氨酸系统。我们将重点关注以下目标，以与中心入门中所述的精神分裂症相关的神经化学失衡的一般模型为指导。 a）继续表征D2激动剂的体内特性； b）开发一种新的D1受体放射性示例，其结合受内源性DA中急性波动的影响； c）开发一种放射性示意剂，该放射性示词标记了我们在其他几个项目中探索的精神分裂症的小鼠模型中应用的NMDA方法的NR2B位点，而f）继续完善我们开发的VoxelWise动力学模型方法。 这些项目共同为精神分裂症研究提供了新的，复杂的工具。在该中心的融资周期中开发的放射性示踪剂和方法将提供给科学界。