Wang Gene-Jack, Chang Linda, Volkow Nora D, Telang Frank, Logan Jean, Ernst Thomas, Fowler Joanna S
Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, NY, USA.
Brain. 2004 Nov;127(Pt 11):2452-8. doi: 10.1093/brain/awh269. Epub 2004 Aug 19.
HIV has a propensity to invade subcortical regions of the brain, which may lead to a subcortical dementia termed HIV-cognitive motor complex. Therefore, we aimed to assess whether dopamine (DA) D2 receptors and transporters (DAT) are affected in the basal ganglia of subjects with HIV, and how these changes relate to dementia status. Fifteen HIV subjects (age 44.5 +/- 11 years; CD4 185 +/- 130/mm3)) and 13 seronegative controls (42 +/- 12 years) were evaluated with PET to assess availability of DAT ([11C]cocaine) and DA D2 receptor ([11C]raclopride). HIV patients with associated dementia (HAD), but not those without dementia (ND) had significantly lower DAT availability in putamen (-19.3%, P = 0.009) and ventral striatum (-13.6%, P = 0.03) compared with seronegative controls. Higher plasma viral load in the HIV dementia patients correlated with lower DAT in the caudate (r = -0.7, P = 0.02) and putamen (r = -0.69, P = 0.03). DA D2 receptor availability, however, showed mild and non-significant decreases in HIV patients. These results provide the first evidence of DA terminal injury in HIV dementia patients, and suggest that decreased DAT may contribute to the pathogenesis of HIV dementia. The greater DAT decrease in the putamen than in the caudate parallels that observed in Parkinson's disease. The inverse relationship between viral burden and DAT availability further supports HIV-mediated neurotoxicity to dopaminergic terminals.
人类免疫缺陷病毒（HIV）易于侵袭大脑皮质下区域，这可能导致一种被称为HIV认知运动复合体的皮质下痴呆。因此，我们旨在评估HIV感染者基底神经节中的多巴胺（DA）D2受体和转运体（DAT）是否受到影响，以及这些变化与痴呆状态有何关联。对15名HIV感染者（年龄44.5±11岁；CD4细胞计数为185±130/mm³）和13名血清学阴性对照者（42±12岁）进行正电子发射断层扫描（PET），以评估DAT（[11C]可卡因）和DA D2受体（[11C]雷氯必利）的可用性。与血清学阴性对照者相比，伴有痴呆的HIV患者（HAD），而非无痴呆的患者（ND），其壳核（-19.3%，P = 0.009）和腹侧纹状体（-13.6%，P = 0.03）中的DAT可用性显著降低。HIV痴呆患者较高的血浆病毒载量与尾状核（r = -0.7，P = 0.02）和壳核（r = -0.69，P = 0.03）中较低的DAT相关。然而，HIV患者的DA D2受体可用性仅呈现轻度且无显著意义的降低。这些结果首次证明了HIV痴呆患者存在DA终末损伤，并表明DAT降低可能参与了HIV痴呆的发病机制。壳核中DAT降低程度大于尾状核，这与帕金森病中观察到的情况相似。病毒载量与DAT可用性之间的负相关进一步支持了HIV介导的对多巴胺能终末的神经毒性作用。
