Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage
Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage
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DOI：
10.3109/13550280903296346
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发表时间：
2009-10-01
影响因子：
3.2
通讯作者：
Rock, R. Bryan
中科院分区：
文献类型：
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作者：
Hu, Shuxian;Sheng, Wen S.;Rock, R. Bryan
已知富含多巴胺（DA）的中脑是人类免疫缺陷病毒(HIV)-1的关键靶点。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主要的破坏，其特征是多巴胺能神经元明显耗损，小胶质细胞激活和反应性星形胶质细胞。利用人类中脑神经元/胶质细胞培养模型，包括多巴胺能神经元、小胶质细胞和星形胶质细胞，实验表征HIV-1 gp120诱导的多巴胺能神经元损伤。通过DA摄取评估功能损害，通过细胞凋亡和氧化损伤评估神经毒性。通过使用这种中脑神经元/胶质培养模型，我们能够确定多巴胺能神经元对gpi20诱导的损伤的相对敏感性，表现为功能降低（DA摄取减少）、形态改变和活力降低。我们还发现gp120诱导的氧化损伤参与了这一神经致病过程。神经病毒学杂志（2009）15,401-410。
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 gpi20-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. Journal of Neuro Virology (2009) 15, 401-410.