STRIATAL NEUROANATOMY IN DOPAMINE TRANSPORTER KNOCKOUT MICE

多巴胺转运蛋白敲除小鼠的纹状体神经解剖学

• 批准号: 8169589
• 负责人: Marc G. Caron
• 金额: $ 4.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169589
• 关键词: Alcohol abuse; Anatomy; Attention deficit hyperactivity disorder; Back; Behavioral Symptoms; Binding Proteins; Brain; Chronic; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Data; Disease; Dopamine; Drug Addiction; Electron Microscopy; Extracellular Space; Funding; Grant; Huntington Disease; Immunohistochemistry; Institution; Knockout Mice; Lead; Magnetic Resonance Imaging; Membrane; Motor; Mus; Nerve; Nerve Degeneration; Neuroanatomy; Neurobiology; Neurons; Neurotransmitters; Parkinson Disease; Pathogenesis; Pharmaceutical Preparations; Research; Research Personnel; Resolution; Resources; Schizophrenia; Source; Symptoms; United States National Institutes of Health; dopamine transporter; extracellular; imaging modality; nerve supply; neuropsychiatry; presynaptic; stimulant abuse

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dopamine is a neurotransmitter that has been implicated in the pathogenesis of several neuropsychiatric disorders, such as Parkinson's disease, schizophrenia, drug and alcohol abuse, Huntington's disease and attention-deficit hyperactivity disorder (ADHD). Dopamine transporter is a membrane-bound protein that reuptakes the released dopamine from the extracellular space back into presynaptic nerve terminals, and is the main regulator extracellular dopamine levels. Mice lacking the dopamine transporter have persistently elevated extracellular dopamine concentrations in the striatum, the main target region of dopaminergic innervation in the brain. In addition to displaying behavioral symptoms reminiscent of chronic psychostimulant abuse and schizophrenia, these mice sporadically develop progressive dyskinetic motor symptoms associated with striatal neurodegeneration resembling Huntingon's disease. The aim of the proposed studies is to investigate in detail the consequences of sustained hyperdopaminergia on striatal neuronal anatomy. This will be accomplished by acquiring and comparing histological data using very high resolution magnetic resonance imaging (MRI) (at 9.4 T), conventional immunohistochemistry, and ultrastructural imaging modalities including electron microscopy. The results will help to understand the effects of chronically high striatal dopamine levels, and may lead to better understanding of neurobiology of schizophrenia, drug addiction and Huntington's disease.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 多巴胺是一种神经递质，与多种神经精神疾病的发病机理有关，例如帕金森氏病，精神分裂症，药物和酒精滥用，亨廷顿氏病以及注意力缺陷多动态障碍（ADHD）。 多巴胺转运蛋白是一种结合膜结合的蛋白，可将释放的多巴胺从细胞外空间重新爆发为突触前神经末端，并且是主要调节剂细胞外多巴胺水平。 缺乏多巴胺转运蛋白的小鼠在纹状体中持续升高细胞外多巴胺浓度，这是大脑中多巴胺能神经支配的主要靶向区域。 除了表现出使人联想到慢性精神刺激性滥用和精神分裂症的行为症状外，这些小鼠偶尔会发展出与纹状体神经变性相关的类似于亨廷顿氏病的进行性运动障碍运动症状。 拟议的研究的目的是详细研究持续性高巴掌能对纹状体神经元解剖结构的后果。 这将通过使用非常高的分辨率磁共振成像（MRI）（9.4 T），常规免疫组织化学以及包括电子显微镜在内的超微结构成像方式来获取和比较组织学数据来实现。 结果将有助于了解慢性纹状体多巴胺水平的影响，并可能使人们更好地了解精神分裂症，吸毒和亨廷顿氏病的神经生物学。