Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, (D-21), P.O. Box 016960, Miami, FL 33101, USA.
J Neurovirol. 2011 Feb;17(1):26-40. doi: 10.1007/s13365-010-0003-4. Epub 2010 Dec 14.
Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2-53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.
人类免疫缺陷病毒（HIV-1）感染中枢神经系统（CNS）与广泛的神经、认知和行为问题有关。HIV-1 在初次感染后很快进入大脑，并以不同的浓度分布在不同的区域，对皮质下区域有特定的亲和力，特别是基底节，导致多巴胺能区域的神经退行性变，并导致中枢神经系统中多巴胺（DA）的可用性降低。尽管有大量关于 HIV-1 相关神经心理学（NP）损害的报道，但很少有研究表明 HIV-1 感染个体死后大脑不同区域多巴胺可用性的降低与生命期间不同 NP 功能的表现水平之间存在直接关系。多巴胺是大脑中的关键神经递质，对运动和边缘功能起调节作用。本研究的目的是调查 HIV/AIDS 个体死后大脑区域（额皮质区域、基底节、尾状核、壳核、苍白球和黑质）中发现的多巴胺可用性降低与不同 NP 功能的生前表现（评估为 T 评分）之间的关系。还研究了不同大脑区域中 HIV-1 RNA 水平与不同 NP 域中表现水平之间的关系。我们发现，尽管与 HIV 阴性对照组相比，接受抗逆转录病毒治疗的 HIV-1 感染个体的大脑区域中的 DA 浓度低 2-53%，但 HIV-1 感染个体黑质（SN）中的 DA 水平降低 45%与信息处理速度、学习、记忆、言语流畅性和跨域平均 T 评分的低表现（T 评分）显著相关。对于高香草酸（HVA），包括黑质、基底节、尾状核和壳核在内的不同区域的可变变化（与 HIV 阴性个体相比）与运动功能、信息处理速度和注意力/工作记忆的表现（T 评分）显著相关。额皮质、尾状核和 GP 中的 HIVRNA 水平与抽象/执行功能、运动、学习、言语流畅性和注意力/工作记忆呈显著负相关。其他大脑区域中的 HIVRNA 与 NP 表现之间无显著相关性。这些发现表明，SN 中多巴胺的可用性降低（中枢神经系统中 DA 合成的主要部位），以及不同大脑区域中 HVA 水平的变化，部分与 HIV/AIDS 个体某些 NP 功能的较低表现水平有关。
