HIV-1 Infection: Central Dopamine and Cognition

HIV-1 感染：中枢多巴胺和认知

• 批准号: 6772442
• 负责人: ADARSH M KUMAR
• 金额: $ 21.59万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772442
• 关键词: AIDS dementia complex; AIDS therapy; HIV infections; antiviral agents; basal ganglia; cerebrospinal fluid; clinical research; cognition; dopamine; frontal lobe /cortex; high performance liquid chromatography; homovanillate; human data; human immunodeficiency virus 1; human tissue; neuroregulation; postmortem; psychomotor function; tissue /cell culture; virus cytopathogenic effect; virus load

DESCRIPTION (provided by applicant): HIV-infection is associated with subcortical type of cognitive dysfunctions and motor disorders. Several lines of evidence suggest that central dopamine deficiency in humans plays an important role in the development of these dysfunctions. These observations have lead to the concept that central dopamine deficiency occurs in HIV-1 infection. Our earlier studies showing a decrease in the levels of dopamine in the cerebrospinal fluid (CSF) of HIV-1+ individuals support this concept. However, the relationship between central dopamine deficiency and cognitive dysfunctions in HIV-1 infection has not been fully investigated. The recent establishment of the NIH sponsored National NeuroAIDS Tissue Consortium (NNTC) has provided an opportunity to test the hypothesis that decreased dopamine levels in various areas of the brain will be related to the cognitive deficits in HIV-1 infection. This application proposes to test this hypothesis by quantifying levels of dopamine and its metabolite, homovanillic acid (HVA), in different areas of the brain of HIV-l+ cases with known cognitive status during life and in HIV-1- cases. It is proposed to investigate samples of brain and CSF obtained from a total of 60 adult men and women, age 19-50 (HIV-I+ cases, N=40; and HIV-1- cases, N=20), belonging to three ethnic groups (Caucasian, African-Americans, Hispanics). The brain tissue from HIV-1+ cases (N=40) will include 10each from those diagnosed with HAD, MCMD, NPI and no cognitive impairment. Tissue samples of the basal ganglia (caudate nucleus and putamen, globus pallidus), substantia nigra, and the frontal cortex, as well as CSF of obtained from the NNTC, and will be assayed for the levels of dopamine and its metabolite, HVA. It is hypothesized that the levels of dopamine and HVA will be decreased in the brain regions ofHIV-1+ cases with cognitive dysfunctions compared to that in HIV-1- cases. This application will also investigate the relationship between central viral load and dopamine/HVA levels, as well as explore the relationship of HAART intervention with dopamine/HVA levels in HIV-1+ individuals. These findings will be helpful in developing therapeutic strategies for interventions.

描述（由申请人提供）：HIV感染与皮质下类型的认知功能障碍和运动障碍有关。几条证据表明，人类中枢多巴胺缺乏在这些功能障碍的发展中起着重要作用。这些观察结果导致了中枢多巴胺缺乏发生在HIV-1感染中的概念。我们早期的研究显示，HIV-1阳性个体的脑脊液（CSF）中多巴胺水平降低，这支持了这一概念。然而，中枢多巴胺缺乏症和HIV-1感染的认知功能障碍之间的关系尚未得到充分研究。最近由美国国立卫生研究院赞助的国家神经艾滋病组织联盟（NNTC）的成立为检验以下假设提供了机会：大脑各区域多巴胺水平的降低与HIV-1感染的认知缺陷有关。本申请提出通过量化在生命期间具有已知认知状态的HIV-1+病例和HIV-1-病例的大脑的不同区域中多巴胺及其代谢物高香草酸（HVA）的水平来测试该假设。拟研究从总共60名年龄19-50岁的成年男性和女性（HIV-1+病例，N=40; HIV-1-病例，N=20）中获得的脑和CSF样本，这些患者属于3个种族组（高加索人、非洲裔美国人、西班牙裔美国人）。来自HIV-1+病例（N=40）的脑组织将包括来自诊断为HAD、MCMD、NPI且无认知障碍的患者的各10份。从NNTC获得基底神经节（尾状核和壳核、苍白球）、黑质和额叶皮质以及CSF的组织样本，并将测定多巴胺及其代谢产物HVA的水平。据推测，与HIV-1-病例相比，具有认知功能障碍的HIV-1+病例的脑区域中多巴胺和HVA水平将降低。本申请还将研究中枢病毒载量与多巴胺/HVA水平之间的关系，以及探索HAART干预与HIV-1+个体中多巴胺/HVA水平的关系。这些发现将有助于制定干预的治疗策略。