Kara Rademeyer, Austin M Jones, Emily A Miller, Daniel Conway, Joseph L McClay, Kurt F Hauser, MaryPeace McRae
{"title":"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","authors":"Kara Rademeyer, Austin M Jones, Emily A Miller, Daniel Conway, Joseph L McClay, Kurt F Hauser, MaryPeace McRae","doi":"10.1007/s13365-025-01252-z","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16665,"journal":{"name":"Journal of NeuroVirology","volume":" ","pages":"242-261"},"PeriodicalIF":1.9000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356723/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differential effects of fentanyl compared to morphine on neuroinflammatory signaling in the brain in EcoHIV-infected mice.\",\"authors\":\"Kara Rademeyer, Austin M Jones, Emily A Miller, Daniel Conway, Joseph L McClay, Kurt F Hauser, MaryPeace McRae\",\"doi\":\"10.1007/s13365-025-01252-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":16665,\"journal\":{\"name\":\"Journal of NeuroVirology\",\"volume\":\" \",\"pages\":\"242-261\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356723/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of NeuroVirology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13365-025-01252-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of NeuroVirology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13365-025-01252-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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.
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.