Methamphetamine stimulates interferon inducible genes in HIV infected brain
Methamphetamine stimulates interferon inducible genes in HIV infected brain
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DOI：
10.1016/j.jneuroim.2005.09.009
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发表时间：
2005-12-30
影响因子：
3.3
通讯作者：
Masliah, E
中科院分区：
文献类型：
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作者：
Everall, I;Salaria, S;Masliah, E
目的：研究人类免疫缺陷病毒(HIV)与甲基苯丙胺的协同作用。设计与方法：利用15例HIV感染者额叶皮质的RNA进行微阵列研究，初步筛选出HIV脑炎(HIVE)差异调控基因。通过对微阵列数据的分析。我们确定了待用定量实时聚合酶链式反应(qRT-PCR)验证的候选基因，并评估这些基因在HIVE和有记录的甲基苯丙胺使用的个体中是否存在差异调节。结果：基因芯片数据分析显示，涉及多个类别的基因在HIVE中表达异常。然后我们选择了15个候选基因进行定量逆转录聚合酶链式反应，并分析了这些基因在三组中的组织浓度：有艾滋病毒感染且无脑病理、有蜂窝者和既有蜂窝且有甲基苯丙胺使用史的人，我们注意到甲基苯丙胺组蜂巢中干扰素诱导基因的上调，作为一个基因组具有非常显著的统计学意义(p=0.0064)。结论：这些发现可能是导致甲基苯丙胺感染者神经变性和神经认知负担加重的致病机制。(C)2005 Elsevier B.V.保留所有权利。
Objective: To study the synergism of HIV and methamphetamine.Design and methods: We undertook a microarray study using RNA from the frontal cortex of 15 individuals with HIV infection to initially identify genes that are differentially regulated by HIV encephalitis (HIVE). From the analysis of the microarray data. we identified candidate genes to be validated by quantitative real time PCR (qRT-PCR) and to assess if these genes were differentially modulated in individuals with HIVE and documented methamphetamine use.Results: Analysis of microarray data revealed that genes involved in several categories were dysregulated in HIVE.. We then chose 15 candidate genes for validation by qRT-PCR and analyzed the tissue concentration of these genes across three groups,: those with HIV infection and no brain pathology, those with HIVE, and those with both HIVE and a history of methamphetamine use, We noted that there was upregulation of interferon inducible genes in the HIVE with methamphetamine using group, which together as a gene group was highly statistically significant (p = 0.0064).Conclusion: These findings indicate that dysregulation of interferon inducible genes may underlie the pathogenic mechanism resulting in greater neurodegenerative and neurocognitive burden that occurs in methamphetamine using HIV infected individuals, (C) 2005 Elsevier B.V. All rights reserved.