AIDS DEMENTIA COMPLEX

该计划项目续签申请概述了一组研究 研究人类重要且有趣的并发症之一 一型免疫缺陷病毒 (HIV-1) 感染、艾滋病痴呆 复合体（ADC），一种表现为皮质下痴呆的病症 特征性认知、运动和行为症状和体征。 虽然被认为很可能是艾滋病毒的根本影响造成的 1、自身感染，而不是来自其他机会性感染，其 发病机制仍远未明确。 中心问题 仍然关注脑功能障碍的本质及其特征 精神运动减慢以及注意力和注意力下降的情况 以及其病毒发病机制。 关于 HIV-1 如何 损伤大脑，推测已转向调用间接机制 涉及神经毒素而不是直接的病毒细胞溶解作用。 探索这些问题的计划分为核心和 4 个 项目： 核心将支持维持一个特征明确的 HIV-1 群体 感染受试者、数据管理单元、临床脑脊液存储库 血液标本、病理标本库。 项目6 将探索评估ADC脑功能障碍的新模式， 专注于持续绩效评估及其与其他方面的关系 神经心理学、电生理学和代谢（PET）测量 ADC 严重性。 项目4使用定量代谢（正电子发射断层扫描， PET）和解剖学（磁共振成像、MRI）措施进行研究 ADC 的病理生理学和潜在可逆性。 项目7采用了结合聚合酶链的新兴技术 基于反应 (PCR) 的原位核酸扩增方法 杂交以确定中枢神经系统中携带 HIV-1 的细胞类型 基因组并确定病毒和病毒的种类和相对丰度 感染和未感染脑细胞中的细胞转录本。 项目 8 探讨了病毒包膜的假定神经毒性作用 糖蛋白，gp120，通过使用开发转基因小鼠模型 细胞特异性启动子控制分泌 gp120 的脑细胞类型。 它还使用神经元毒性的体外模型来探索是否 不同病毒分离株的 gp120 在以下方面有所不同 神经毒性。

This Program Project renewal application outlines a group of studies investigating one of the important and intriguing complications of human immunodeficiency virus type one (HIV-1) infection, the AIDS dementia complex (ADC), a condition manifesting as a subcortical dementia with characteristic cognitive, motor and behavioral symptoms and signs. While considered to most likely result from a fundamental effect of HIV- 1, itself, rather than from another, opportunistic infection, its pathogenesis is still far from clearly understood. Central questions remain regarding the nature of brain dysfunction with its characteristic profile of psychomotor slowing and reduced attention and concentration as well as regarding its viral pathogenesis. With respect to how HIV-1 injures the brain, speculation has turned to invoke indirect mechanisms involving neurotoxins rather than direct viral cytolysis. The Program exploring these issues is organized into a Core and 4 Projects: The Core will support maintenance of a well-characterized group of HIV-1 infected subjects, a data management unit, a repository for clinical CSF and blood specimens, and a pathological specimen library. Project 6 will explore new modes of evaluating the cerebral dysfunction of ADC, focusing on continuous performance assessment and its relation to other neuropsychological, electrophysiological and metabolic (PET) measures of ADC severity. Project 4 uses quantitative metabolic (positron emission tomography, PET) and anatomic (magnetic resonance imaging, MRI) measures to study the pathophysiology and potential reversibility of ADC. Project 7 uses the emerging technology combining polymerase chain reaction (PCR)-based nucleic acid amplification methods with in situ hybridization to define the types of cells in the CNS that harbor HIV-1 genomes and to determine the kind and relative abundance of viral and cellular transcripts in infected and uninfected brain cells. Project 8 addresses the putative neurotoxic role of the viral envelope glycoprotein, gp120, by development of transgenic mouse models using cell-specific promoters to control the brain cell type secreting gp120. It also uses in vitro models of neuronal toxicity to explore whether gp120 from different viral isolates varies with respect to neurotoxicity.