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感染与皮层类型的认知功能障碍和运动障碍有关。几条证据表明，人类中央多巴胺缺乏症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一个概念，即HIV-1感染中央多巴胺缺乏症发生。我们较早的研究表明，HIV-1+个体的脑脊液（CSF）中多巴胺水平降低了这一概念。然而，尚未对HIV-1感染中中央多巴胺缺乏症与认知功能障碍之间的关系。 NIH赞助的国家神经辅助组织（NNTC）的最新建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降低将与HIV-1感染中的认知缺陷有关。该应用建议通过量化多巴胺的水平及其代谢产物（HVA）的水平，在HIV-L+病例的不同区域，在生命中和HIV-1-病例中具有已知认知状态。有人建议研究从总共60名成年男性和女性获得的大脑和CSF样本，年龄在19-50岁（HIV-I+病例，n = 40;和HIV-1-病例，n = 20），属于三个族裔（高加索人，非裔美国人，西班牙裔）。来自HIV-1+病例的脑组织（n = 40）将包括10个被诊断为HAT，MCMD，NPI和无认知障碍的人。基底神经节的组织样品（尾状核和壳核，果胶pallidus），黑质Nigra和额叶皮质以及从NNTC获得的CSF，并将分析多巴胺及其代谢物HVA的水平。假设与HIV-1-病例相比，在HIV-1+病例的大脑区域中，多巴胺和HVA的水平将降低。该应用还将研究中央病毒载量与多巴胺/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措施的治疗策略。