AIDS DEMENTIA COMPLEX

此计划项目更新申请概述了一组研究 研究人类重要而有趣的并发症之一， 免疫缺陷病毒1型（HIV-1）感染，艾滋病痴呆 复杂（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。 虽然被认为最有可能是由艾滋病毒的根本影响造成的- 1、本身，而不是从另一个，机会性感染，其 发病机制仍远未被清楚地理解。 核心问题 关于脑功能障碍的性质， 注意力和集中力减缓和降低的心理特征 以及关于其病毒发病机理的研究。 关于HIV-1如何 会伤害大脑，人们开始猜测 涉及神经毒素而不是直接的病毒细胞溶解。 探索这些问题的方案分为核心方案和4个方案。 项目： 核心方案将支持维持一个特征明确的HIV-1感染者群体， 感染受试者，数据管理单元，临床CSF储存库 血液标本和病理标本库。 Project 6 将探索新的模式来评估ADC的脑功能障碍， 注重持续的业绩评估及其与其他 神经心理学、电生理学和代谢（PET）测量， ADC严重度。 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）测量研究 ADC的病理生理学和潜在可逆性。 项目7使用新兴技术结合聚合酶链 基于原位反应（PCR）的核酸扩增方法 杂交以确定CNS中携带HIV-1的细胞类型 基因组，并确定病毒的种类和相对丰度， 受感染和未受感染的脑细胞中的细胞转录物。 项目8讨论了病毒包膜的假定神经毒性作用 糖蛋白，gp 120，通过开发转基因小鼠模型， 细胞特异性启动子来控制分泌GP 120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 来自不同病毒分离株的gp 120在以下方面不同： 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.