AIDS DEMENTIA COMPLEX

本计划项目续签申请概述了一组研究 研究人类重要而耐人寻味的并发症之一 艾滋病痴呆与免疫缺陷病毒1型感染 复合体(ADC)，表现为皮质下痴呆 具有认知、运动和行为特征的症状和体征。 虽然被认为最有可能是艾滋病毒的根本影响造成的- 1本身，而不是来自另一个机会性感染，它的 其发病机制目前尚不清楚。中心问题 关于脑功能障碍的本质及其特点 精神运动减慢、注意力和注意力减退的特征 以及它的病毒致病机制。关于HIV-1是如何 损伤大脑，投机转向调用间接机制 涉及神经毒素而不是直接的病毒细胞溶解。 探索这些问题的计划被组织成核心和4个 项目： 该核心将支持维持一组特征良好的艾滋病毒-1病毒 感染对象、数据管理单元、临床脑脊液储存库 和血液样本，以及病理标本库。项目6 将探索评估ADC脑功能障碍的新模式， 注重持续绩效考核及其与其他绩效考核的关系 神经心理、电生理和代谢(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)措施研究 ADC的病理生理学和潜在的可逆性。 项目7使用了结合聚合酶链条的新兴技术 基于聚合酶链式反应的核酸原位扩增方法 用杂交法确定中枢神经系统中携带HIV-1的细胞类型 并确定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解决了病毒包膜可能的神经毒性作用。 糖蛋白gp120，通过建立转基因小鼠模型 控制脑细胞类型分泌gp120的细胞特异性启动子。 它还使用神经元毒性的体外模型来探索 来自不同病毒分离株的gp120在以下方面存在差异 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.