芬太尼与吗啡对ecohiv感染小鼠大脑中神经炎症信号的不同影响

IF 1.9 4区 医学 Q3 NEUROSCIENCES
Journal of NeuroVirology Pub Date : 2025-06-01 Epub Date: 2025-05-30 DOI:10.1007/s13365-025-01252-z
Kara Rademeyer, Austin M Jones, Emily A Miller, Daniel Conway, Joseph L McClay, Kurt F Hauser, MaryPeace McRae
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引用次数: 0

摘要

艾滋病毒相关的神经认知障碍(HAND)带来了重大挑战,特别是在患有合并症阿片类药物使用障碍(OUD)的个体中。芬太尼是一种强效的合成阿片类药物,是阿片类药物相关死亡的主要原因,但其对艾滋病毒的影响仍知之甚少。本研究研究了芬太尼和吗啡对ecohiv感染小鼠的神经炎症信号、血脑屏障(BBB)完整性和抗逆转录病毒(ARV)脑积累的不同影响。C57BL/6小鼠分为吗啡、芬太尼或生理盐水治疗组,有无EcoHIV感染。采用ELISA法检测纹状体和海马组织紧密连接蛋白claudin-5和ZO-1的含量,采用多元法检测促炎趋化因子的含量。在感染ecohiv的小鼠中,两种阿片类药物都显著增加纹状体中CCL2、CCL4、CCL5和CCL11的浓度,芬太尼引起CCL2的增加比吗啡更大。此外,芬太尼显著降低纹状体CCL3浓度,而吗啡不显著降低。主成分分析揭示了纹状体中不同的治疗特异性模式,强调了阿片类药物特异性差异。紧密连接蛋白的表达数据显示了阿片特异性、性别特异性和区域特异性对血脑屏障关键蛋白ZO-1和claudin-5的影响。这两种阿片类药物也降低了感染小鼠的ARV脑浓度,具有区域和阿片类药物特异性作用。芬太尼减少了海马区的多替格拉韦,而吗啡减少了两个区域的阿巴卡韦。这些发现表明,芬太尼和吗啡暴露在HIV背景下对神经炎症反应、血脑屏障完整性和ARV脑暴露产生不同的影响。了解这些阿片类药物特异性作用对于改善艾滋病毒和OUD患者的临床结果和治疗策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.

Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.

Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.

Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.

HIV-associated neurocognitive disorders (HAND) pose significant challenges, particularly in individuals with comorbid opioid use disorder (OUD). Fentanyl, a potent synthetic opioid, is a leading contributor to opioid-related fatalities, yet its effects in the context of HIV remain poorly understood. This study investigated the differential impacts of fentanyl and morphine on neuroinflammatory signaling, blood-brain barrier (BBB) integrity, and antiretroviral (ARV) brain accumulation in EcoHIV-infected mice. C57BL/6 mice were assigned to morphine, fentanyl, or saline treatment groups, with or without EcoHIV infection. Tight junction proteins claudin-5 and ZO-1 were measured in striatum and hippocampus via ELISA, while proinflammatory chemokines were analyzed by multiplex assay. In EcoHIV-infected mice, both opioids significantly increased CCL2, CCL4, CCL5, and CCL11 concentrations in the striatum, with fentanyl causing greater increases in CCL2 than morphine. Additionally, fentanyl, but not morphine, significantly decreased CCL3 concentrations in the striatum. Principal component analysis revealed distinct treatment-specific patterns within the striatum, underscoring opioid-specific differences. Tight junction protein expression data demonstrate opioid-specific, sex-specific, and region-specific effects on the key BBB proteins, ZO-1 and claudin-5. Both opioids also reduced ARV brain concentrations in infected mice, with region- and opioid-specific effects. Fentanyl decreased dolutegravir in the hippocampus, while morphine decreased abacavir in both regions. These findings demonstrate that fentanyl and morphine exposure in the context of HIV produce distinct impacts on neuroinflammatory response, BBB integrity, and ARV brain exposure. Understanding these opioid-specific effects is critical for improving clinical outcomes and treatment strategies for individuals with HIV and OUD.

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来源期刊
Journal of NeuroVirology
Journal of NeuroVirology 医学-病毒学
CiteScore
6.60
自引率
3.10%
发文量
77
审稿时长
6-12 weeks
期刊介绍: The Journal of NeuroVirology (JNV) provides a unique platform for the publication of high-quality basic science and clinical studies on the molecular biology and pathogenesis of viral infections of the nervous system, and for reporting on the development of novel therapeutic strategies using neurotropic viral vectors. The Journal also emphasizes publication of non-viral infections that affect the central nervous system. The Journal publishes original research articles, reviews, case reports, coverage of various scientific meetings, along with supplements and special issues on selected subjects. The Journal is currently accepting submissions of original work from the following basic and clinical research areas: Aging & Neurodegeneration, Apoptosis, CNS Signal Transduction, Emerging CNS Infections, Molecular Virology, Neural-Immune Interaction, Novel Diagnostics, Novel Therapeutics, Stem Cell Biology, Transmissable Encephalopathies/Prion, Vaccine Development, Viral Genomics, Viral Neurooncology, Viral Neurochemistry, Viral Neuroimmunology, Viral Neuropharmacology.
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