HIV-1 Infection: Central Dopamine and Cognition

HIV-1 感染：中枢多巴胺和认知

• 批准号: 6916386
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916386
• 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感染与皮层下型认知功能障碍和运动障碍相关。一些证据表明，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在HIV-1感染中发生中枢多巴胺缺乏的概念。我们早期的研究表明，HIV-1+个体脑脊液（CSF）中多巴胺水平的降低支持了这一概念。然而，HIV-1感染中枢性多巴胺缺乏与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成立的国家神经艾滋病组织联盟（NNTC）提供了一个测试假设的机会，即大脑各区域多巴胺水平的降低将与HIV-1感染的认知缺陷有关。本应用程序提出通过量化多巴胺及其代谢物同质香草酸（HVA）的水平来验证这一假设，在已知认知状态的HIV-1 +病例和HIV-1病例的大脑不同区域。本研究拟对60名年龄在19-50岁的成年男性和女性（HIV-1 +病例，N=40； HIV-1病例，N=20）的脑和脑脊液样本进行研究，这些样本属于三个种族群体（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10个来自被诊断为HAD、MCMD、NPI和无认知障碍的患者。从NNTC获得基底神经节（尾状核、壳核、白球）、黑质、额叶皮层以及脑脊液的组织样本，并将检测多巴胺及其代谢物HVA的水平。据推测，与HIV-1患者相比，HIV-1阳性认知功能障碍患者大脑区域的多巴胺和HVA水平会降低。本应用程序还将研究中心病毒载量与多巴胺/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。