ArticleJournal of neuroinflammation2018
A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.Biomedicines · 2025Review
- Recent advances in nanotherapeutics for HIV-associated neurocognitive disorders and substance use disorders.Nanomedicine (London, England) · 2025Review
- Article
- The contributing role of CCR5 in dementia.Frontiers in neurology · 2025Review
- Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial cocultures through actions independent of opioid receptors.Journal of neurophysiology · 2024Article
- Molecular Role of HIV-1 Human Receptors (CCL5-CCR5 Axis) in neuroAIDS: A Systematic Review.Microorganisms · 2024Review
- Biosafety and mental health: Virus induced cognitive decline.Biosafety and health · 2023Review
- HIV-1 gp120 protein promotes HAND through the calcineurin pathway activation.Mitochondrion · 2023Article
- Article
- Accelerated brain aging with opioid misuse and HIV: New insights on the role of glially derived pro-inflammation mediators and neuronal chloride homeostasis.Current opinion in neurobiology · 2023Review
- Astrocytes: Role in pathogenesis and effect of commonly misused drugs in the HIV infected brain.Current research in neurobiology · 2023Review
- HIV-1 and opiates modulate miRNA profiles in extracellular vesicles.Frontiers in immunology · 2023Article
- Review
- Review
- Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques.Frontiers in neuroscience · 2022Article
- Neurodegeneration Within the Amygdala Is Differentially Induced by Opioid and HIV-1 Tat Exposure.Frontiers in neuroscience · 2022Article
- Drugs of Abuse and Their Impact on Viral Pathogenesis.Viruses · 2021Review
- CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice.Molecular neurodegeneration · 2021Article
- 7,8-Dihydroxyflavone improves neuropathological changes in the brain of Tg26 mice, a model for HIV-associated neurocognitive disorder.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe collective cognitive and motor deficits known as HIV-associated neurocognitive disorders (HAND) remain high even among HIV+ individuals whose antiretroviral therapy is optimized. HAND is worsened in the context of opiate abuse. The mechanism of exacerbation remains unclear but likely involves chronic immune activation of glial cells resulting from persistent, low-level exposure to the virus and viral proteins. We tested whether signaling through C-C chemokine receptor type 5 (CCR5) contributes to neurotoxic interactions between HIV-1 transactivator of transcription (Tat) and opiates and explored potential mechanisms.
methodsNeuronal survival was tracked in neuronal and glial co-cultures over 72 h of treatment with HIV-1 Tat ± morphine using cells from CCR5-deficient and wild-type mice exposed to the CCR5 antagonist maraviroc or exogenously-added BDNF (analyzed by repeated measures ANOVA). Intracellular calcium changes in response to Tat ± morphine ± maraviroc were assessed by ratiometric Fura-2 imaging (analyzed by repeated measures ANOVA). Release of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF from CCR5-deficient and wild-type glia was measured by ELISA (analyzed by two-way ANOVA). Levels of CCR5 and μ-opioid receptor (MOR) were measured by immunoblotting (analyzed by Student's t test).
resultsHIV-1 Tat induces neurotoxicity, which is greatly exacerbated by morphine in wild-type cultures expressing CCR5. Loss of CCR5 from glia (but not neurons) eliminated neurotoxicity due to Tat and morphine interactions. Unexpectedly, when CCR5 was lost from glia, morphine appeared to entirely protect neurons from Tat-induced toxicity. Maraviroc pre-treatment similarly eliminated neurotoxicity and attenuated neuronal increases in [Ca
conclusionsOur results suggest a critical role for glial CCR5 in mediating neurotoxic effects of HIV-1 Tat and morphine interactions on neurons. A shift in the proBDNF/BDNF ratio that favors neurotrophic support may occur when glial CCR5 signaling is blocked. Some neuroprotection occurred only in the presence of morphine, suggesting that loss of CCR5 may fundamentally change signaling through the MOR in glia.
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