HIV-1 Infection: Central Dopamine and Cognition

HIV-1 感染：中枢多巴胺和认知

• 批准号: 6696528
• 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/6696528
• 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。多项证据表明，人类中枢多巴胺缺乏在这些功能障碍的发生中起着重要作用。这些观察结果得出这样一个概念：HIV-1 感染中会出现中枢多巴胺缺乏。我们早期的研究表明，HIV-1+ 个体的脑脊液 (CSF) 中多巴胺水平下降，支持了这一观点。然而，中枢多巴胺缺乏与 HIV-1 感染认知功能障碍之间的关系尚未得到充分研究。最近由 NIH 资助的国家神经艾滋病组织联盟 (NNTC) 的成立提供了一个机会来检验以下假设：大脑各个区域的多巴胺水平下降与 HIV-1 感染的认知缺陷有关。本申请提出通过量化生前认知状态已知的HIV-1+病例和HIV-1-病例的大脑不同区域中多巴胺及其代谢物高香草酸(HVA)的水平来检验该假设。建议调查从 60 名年龄在 19-50 岁的成年男性和女性（HIV-I+病例，N=40；和 HIV-1-病例，N=20）中获得的脑部和脑脊液样本，这些样本属于三个种族群体（白人、非裔美国人、西班牙裔）。 HIV-1+ 病例 (N=40) 的脑组织将包括诊断为 HAD、MCMD、NPI 且无认知障碍的患者各 10 个。从 NNTC 获取基底神经节（尾状核和壳核、苍白球）、黑质和额叶皮层的组织样本以及脑脊液，用于检测多巴胺及其代谢物 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+ 病例的大脑区域中多巴胺和 HVA 的水平会降低。该应用还将研究中心病毒载量与多巴胺/HVA水平之间的关系，并探讨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治疗策略。