Turchan J, Anderson C, Hauser K F, Sun Q, Zhang J, Liu Y, Wise P M, Kruman I, Maragos W, Mattson M P, Booze R, Nath A
Department of Neurology, University of Kentucky, Lexington, USA.
BMC Neurosci. 2001;2:3. doi: 10.1186/1471-2202-2-3. Epub 2001 Mar 2.
Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.
Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors.
Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.
在药物滥用者中，尤其是女性，人类免疫缺陷病毒（HIV）感染率仍在以惊人的速度上升。滥用药物会对大脑造成持久损害，而HIV感染常常导致痴呆症。为了确定这些药物如何与HIV相互作用导致中枢神经系统损伤，我们使用了一种体外人类神经元培养物，其特征在于存在多巴胺能受体、转运体和雌激素受体。我们确定了多巴胺能药物、甲基苯丙胺或可卡因与神经毒性HIV蛋白gp120和Tat的联合作用。
通过线粒体膜电位变化和神经元细胞死亡来衡量，急性暴露于这些物质会导致协同神经毒性反应。神经毒性发生在神经元的一个亚群中。重要的是，17β-雌二醇的存在可预防这些协同神经毒性，并且神经保护作用部分由雌激素受体介导。
我们的观察结果表明，甲基苯丙胺和可卡因可能会影响HIV痴呆症的病程，此外还表明雌激素可改变HIV与药物的相互作用。
