HIV-1转基因大鼠吗啡耐受性中阿片依赖基因和信号通路的性别依赖调节。

IF 1.9 4区 医学 Q3 NEUROSCIENCES
Journal of NeuroVirology Pub Date : 2025-06-01 Epub Date: 2025-05-07 DOI:10.1007/s13365-025-01257-8
Muhammed Bishir, Wenfei Huang, Ilker K Sariyer, Sulie L Chang
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引用次数: 0

摘要

滥用阿片类药物是艾滋病毒感染者(PWH)的主要合并症。PWH中的神经异常和阿片类药物成瘾涉及信号通路之间的相互作用。然而,HIV蛋白对吗啡依赖的影响尚未得到充分研究。我们旨在了解PWH的纹状体(Str)和前额叶皮质(PFC)中阿片依赖基因和信号通路的调节。HIV-1转基因(HIV-1Tg)大鼠和F344对照动物分别于第1天和第2天皮下注射吗啡2粒和4粒(75 mg/粒)/安慰剂。第5天,吗啡耐受时处死大鼠,收集Str和PFC进行RNA分离和cDNA制备。采用pcr阵列检测65个阿片类药物依赖基因的表达。吗啡处理大鼠Str和PFC中不同数量的基因显著上调。将折叠变化值上传到QIAGEN Ingenuity Pathway Analysis,以研究与处理条件相关的信号通路。注射吗啡后,雄性和雌性HIV-1Tg大鼠Str神经元中CREB信号通路和神经炎症信号通路高度激活。注射吗啡后,雌性HIV-1Tg大鼠的Gαq信号和S100家族信号被激活。同样,在PFC中,IP3的合成、神经元的CREB信号、雄性的Gαq信号、神经元的CREB信号和雌性的Gαq信号被激活。通过生物信息学分析,我们确定了吗啡耐受时HIV-1Tg大鼠阿片依赖基因表达和途径富集的关键信号通路和性别依赖性变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gender dependent modulation of opioid dependance genes and signaling pathways in HIV-1 Transgenic rats at morphine tolerance.

Misuse of opioids is a major comorbidity in people with HIV (PWH). Neurological abnormalities and opioid addiction seen in PWH involve the interplay among signaling pathways. However, the impact of HIV proteins on morphine dependence is understudied. We aimed to understand the modulation of the opioid dependence genes and signaling pathways in the striatum (Str) and prefrontal cortex (PFC) of PWH. HIV-1 transgenic (HIV-1Tg) rats and F344 control animals were given 2 and 4 pellets of morphine (75-mg/pellet)/placebo on Days 1 and 2, respectively, via subcutaneous implantation. On Day 5, at morphine tolerance the rats were sacrificed, Str and PFC were collected for RNA isolation and cDNA preparation. A PCR-array was used to examine the expression of the 65 opioid dependance genes. Varying numbers of genes were significantly upregulated in the Str and PFC of morphine treated rats. Fold change values were uploaded to QIAGEN Ingenuity Pathway Analysis, to study the signaling pathways associated with the treatment conditions. CREB signaling in neurons and Neuroinflammation signaling pathway were highly activated in the Str of both male and female HIV-1Tg rats given morphine. Gαq signaling and S100 family signaling were activated in female HIV-1Tg rats received morphine. Similarly, in the PFC, synthesis of IP3, CREB Signaling in neurons, Gαq signaling in males and CREB Signaling in neuron, and Gαq signaling in females were activated. Using bioinformatic analysis, we identified key signaling pathways and gender dependent changes in the opioid dependent gene expression and pathway enrichment of HIV-1Tg rats at morphine tolerance.

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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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