Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders.

Novel RNA-Seq Signatures Post-Methamphetamine and Oxycodone Use in a Model of HIV-Associated Neurocognitive Disorders.
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DOI:
10.3390/v15091948
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发表时间:
2023-09-19
期刊:
Viruses
影响因子:
--
通讯作者:
Pendyala G
Pendyala G
中科院分区:
其他
文献类型:
--
作者:
Athota P;Nguyen NM;Schaal VL;Jagadesan S;Guda C;Yelamanchili SV;Pendyala G

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在21世纪世纪,由于抗逆转录病毒疗法(ART)的发展,HIV相关神经认知障碍(HAND)的影响在个体中已显著降低。然而,日益流行的多物质使用(PSU)已导致关注PSU对HIV血清阳性个体的影响。为了有效地治疗受HAND影响的个体,了解PSU影响的生物学机制至关重要,包括识别新的标志物。为了填补这一重要的知识空白,我们使用体内HIV-1转基因(HIV-1 Tg)动物模型来研究慢性甲基苯丙胺(METH)和羟考酮(oxy)联合使用的效果。对纹状体的RNA-Seq分析-主要由HIV和滥用药物靶向的大脑区域-确定了METH和oxy暴露后的关键差异表达标记。此外,CNOGO分析和免疫途径分析(IPA)揭示了与ATP激活的腺苷受体、神经肽激素活性和催产素信号通路相关的关键分子和生物学功能在不同治疗组之间发生改变。目前的研究进一步揭示了慢性PSU和HIV感染的有害影响,这些影响随后会影响患有HAND的多物质使用者的神经系统结果。
In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU, including the identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-1 Transgenic (HIV-1 Tg) animal model to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). A RNA-Seq analysis on the striatum—a brain region that is primarily targeted by both HIV and drugs of abuse—identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptors, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.
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