ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Morphine increases brain levels of ferritin heavy chain leading to inhibition of CXCR4-mediated survival signaling in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
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- CXCL14 as a Key Regulator of Neuronal Development: Insights from Its Receptor and Multi-Omics Analysis.International journal of molecular sciences · 2024Article
- The Endolysosomal Transporter DMT1 is Required for Morphine Regulation of Neuronal Ferritin Heavy Chain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- The US9-Derived Protein gPTB9TM Modulates APP Processing Without Targeting Secretase Activities.Molecular neurobiology · 2023Article
- Attenuated initial serum ferritin concentration in critically ill coronavirus disease 2019 geriatric patients with comorbid psychiatric conditions.Frontiers in psychiatry · 2022Article
- Reactive Oxygen Species (ROS) are Critical for Morphine Exacerbation of HIV-1 gp120-Induced Pain.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Characterization of functional protein complexes from Alzheimer's disease and healthy brain by mass spectrometry-based proteome analysis.Scientific reports · 2021Article
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Homocysteine-induced decrease in HUVEC cells' resistance to oxidative stress is mediated by Akt-dependent changes in iron metabolism.European journal of nutrition · 2021Article
- Cellular iron storage and trafficking are affected by GTN stimulation in primary glial and meningeal cell culture.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Ferritins in Kidney Disease.Seminars in nephrology · 2020Review
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- Bidirectional Regulation of Opioid and Chemokine Function.Frontiers in immunology · 2020Review
- The functional microscopic neuroanatomy of the human subthalamic nucleus.Brain structure & function · 2019Article
- Hyperactivity, dopaminergic abnormalities, iron deficiency and anemia in an in vivo opioid receptors knockout mouse: Implications for the restless legs syndrome.Behavioural brain research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
This study focuses on the effect of mu-opioid receptor agonists on CXCR4 signaling in neurons and the mechanisms involved in regulation of neuronal CXCR4 by opiates. The data show that CXCR4 is negatively modulated by long-term morphine treatments both in vitro and in vivo; CXCR4 inhibition is caused by direct stimulation of mu-opioid receptors in neurons, leading to alterations of ligand-induced CXCR4 phosphorylation and upregulation of protein ferritin heavy chain (FHC), a negative intracellular regulator of CXCR4. Reduced coupling of CXCR4 to G-proteins was found in the brain of morphine-treated rats, primarily cortex and hippocampus. CXCR4-induced G alpha(i)/G betagamma activities were suppressed after 24 h treatment of cortical neurons with morphine or the selective mu-opioid agonist DAMGO (D-Ala2-N-Me-Phe(4)-glycol(5)-enkephalin), as shown by analysis of downstream targets of CXCR4 (i.e., cAMP, Akt, and ERK1/2). These agonists also prevented CXCL12-induced phosphorylation of CXCR4, indicating a deficit of CXCR4 activation in these conditions. Indeed, morphine (or DAMGO) inhibited prosurvival signaling in neurons. These effects are not attributable to a reduction in CXCR4 expression or surface levels but rather to upregulation of FHC by opioids. The crucial role of FHC in inhibition of neuronal CXCR4 was confirmed by in vitro and in vivo RNA interference studies. Overall, these findings suggest that opiates interfere with normal CXCR4 function in the brain. By this mechanism, opiates could reduce the neuroprotective functions of CXCR4 and exacerbate neuropathology in opiate abusers who are affected by neuroinflammatory/infectious disorders, including neuroAIDS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.