Center for Infectious Diseases and Microbiology Translational Research, Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
J Neurovirol. 2009 Sep;15(5-6):401-10. doi: 10.3109/13550280903296346.
The dopamine (DA)-rich midbrain is known to be a key target of human immunodeficiency virus (HIV)-1. Studies of simian immunodeficiency virus (SIV)-induced neuropathogenesis recently established that there is a major disruption within the nigrostriatal dopaminergic system characterized by marked depletion of dopaminergic neurons, microglial cell activation, and reactive astrocytes. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, experiments were performed to characterize the damage to dopaminergic neurons induced by HIV-1 gp120. Functional impairment was assessed by DA uptake, and neurotoxicity was measured by apoptosis and oxidative damage. Through the use of this mesencephalic neuronal/glial culture model, we were able to identify the relative sensitivity of dopaminergic neurons to gp120-induced damage, manifested as reduced function (decreased DA uptake), morphological changes, and reduced viability. We also showed that gp120-induced oxidative damage is involved in this neuropathogenic process.
富含多巴胺（DA）的中脑是人类免疫缺陷病毒（HIV-1）的主要靶标。最近对猴免疫缺陷病毒（SIV）诱导的神经发病机制的研究表明，黑质纹状体多巴胺能系统存在严重破坏，表现为多巴胺能神经元明显耗竭、小胶质细胞激活和反应性星形胶质细胞。使用含有多巴胺能神经元、小胶质细胞和星形胶质细胞的人胚胎中脑神经/神经胶质培养模型，进行了实验以表征 HIV-1 gp120 诱导的多巴胺能神经元损伤。通过 DA 摄取评估功能障碍，通过细胞凋亡和氧化损伤测量神经毒性。通过使用这种中脑神经/神经胶质培养模型，我们能够确定多巴胺能神经元对 gp120 诱导的损伤的相对敏感性，表现为功能降低（DA 摄取减少）、形态变化和活力降低。我们还表明，gp120 诱导的氧化损伤参与了这一神经发病过程。
