Methamphetamine/SIV Interaction in the CNS

甲基苯丙胺/SIV 在中枢神经系统中的相互作用

基本信息

批准号：
7884107
负责人：
HOWARD S FOX
金额：
$ 21.61万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7884107
关键词：
AIDS Dementia Complex AIDS neuropathy Acquired Immunodeficiency Syndrome Acute Address Adherence Affect Animal Model Animals Area Autophagocytosis Biochemical Brain Brain Injuries Cell Survival Central Nervous System Diseases Cessation of life Chronic Cognition Disorders Cognitive Control Animal Data Dementia Disease Disease Progression Dose Drug usage Enrollment Exhibits Functional disorder Genetic HIV HIV-1 Housekeeping Human Immune Immune system In Vitro Incidence Individual Infection Investigation Life Macaca mulatta Methamphetamine Microglia Minor Modeling Monkeys Needle Sharing Nerve Degeneration Nervous System Trauma Neuraxis Neurons Neurotoxicity Syndromes Organ Pathology Pharmaceutical Preparations Physiological Placebos Population Prevalence Process Protocols documentation Regimen Risk SIV Sex Behavior Site Staging System Systemic disease T-Lymphocyte Testing Therapeutic Toxic effect Viral Load result Viremia Virus Diseases Work body system brain tissue dopaminergic neuron drug abuser drug of abuse high risk in vitro Model insight macrophage mortality motor disorder motor impairment multiple drug use neuronal survival neurotoxic nonhuman primate pre-clinical psychostimulant treatment strategy virus host interaction

项目摘要

DESCRIPTION (provided by applicant): Drugs of abuse are known to be a significant co-factor in HIV infection. However addressing whether drugs of abuse are significant co-factors in disease progression has been difficult. Methamphetamine (METH) is a frequently and increasingly used drug among those infected with HIV, and those at high risk for becoming HIV infected. Our Preliminary Data indicates that METH can negatively affect many parameters of simian immunodeficiency virus (SIV)-induced disease in monkeys. Here we proposed a well- powered study to obtain definitive results on the interaction of METH and SIV. Our hypothesis is that there are distinct areas of interaction occur between these agents that combine to increase disease. First, there is a combined toxic effect in the central nervous system (CNS), in which SIV and METH combine to yield functional and biochemical deficits both greater and different than either agent alone. Second, there is an interaction in the immune system that affects disease course and likely secondarily the CNS. Third, both SIV and METH affect autophagy, an essential process in neurons whose disruption leads to neuronal damage, and the effects of SIV and METH together are greater than either alone. Pharmacological agents that affect autophagy will be tested in a preclinical setting to provide both mechanistic insights and provide leads for treatment strategies. Those infected with HIV, and those at high risk for HIV infection, include people that frequently use drugs of abuse, including methamphetamine, the use of which is increasing nationwide. Methamphetamine can damage the brain, as can HIV infection. Here we will examine how these two agents interact to cause brain as well as other problems, and such work will provide insight into not only these two agents, but means to protect neurons from other damaging processes.

描述（由申请人提供）：已知滥用药物是 HIV 感染的重要辅助因素。然而，解决滥用药物是否是疾病进展的重要辅助因素一直很困难。甲基苯丙胺 (METH) 是一种在 HIV 感染者和 HIV 感染高危人群中经常使用且越来越多使用的药物。我们的初步数据表明，冰毒会对猿猴免疫缺陷病毒 (SIV) 诱发的猴子疾病的许多参数产生负面影响。在这里，我们提出了一项强有力的研究，以获得关于 METH 和 SIV 相互作用的明确结果。我们的假设是，这些药物之间存在不同的相互作用领域，这些相互作用共同增加了疾病的发生。首先，在中枢神经系统（CNS）中存在联合毒性作用，其中SIV和METH结合产生比单独使用任一药物更大且不同的功能和生化缺陷。其次，免疫系统中存在相互作用，影响疾病进程，其次可能影响中枢神经系统。第三，SIV 和 METH 都会影响自噬，这是神经元中的一个重要过程，其破坏会导致神经元损伤，并且 SIV 和 METH 一起的影响比单独使用任何一个都更大。影响自噬的药物将在临床前环境中进行测试，以提供机制见解并为治疗策略提供线索。艾滋病毒感染者和艾滋病毒感染高危人群包括经常使用滥用药物的人，其中包括甲基苯丙胺，其使用量在全国范围内不断增加。甲基苯丙胺和艾滋病毒感染都会损害大脑。在这里，我们将研究这两种药物如何相互作用导致大脑以及其他问题，这样的工作不仅将提供对这两种药物的深入了解，而且还将提供保护神经元免受其他破坏过程的方法。