ArticlePloS one2011
Toll-like receptor 9 is required for opioid-induced microglia apoptosis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 97 citations in OpenAlex.
- Prescription Opioids and Risk of Dementia or Cognitive Decline: A Prospective Cohort Study.Journal of the American Geriatrics Society · 2015Trial
- Modulation of immune responses by opioids through toll-like and P2X receptor signaling in COVID-19.Purinergic signalling · 2026Review
- Morphine-mediated release of astrocyte-derived extracellular vesicle miR-23a induces loss of pericyte coverage at the blood-brain barrier: Implications for neuroinflammation.Frontiers in cell and developmental biology · 2022Article
- μ-Opioid Receptor-Mediated AT1R-TLR4 Crosstalk Promotes Microglial Activation to Modulate Blood Pressure Control in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2021Article
- Review
- Nucleic Acid Sensors and Programmed Cell Death.Journal of molecular biology · 2020Review
- Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review.Molecular neuropsychiatry · 2019Review
- Lic regulates JNK-mediated cell death in Drosophila.Cell proliferation · 2019Article
- Neurobiological Effects of Morphine after Spinal Cord Injury.Journal of neurotrauma · 2017Article
- Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Review
- Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.Frontiers in molecular neuroscience · 2017Review
- Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Article
- Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.PloS one · 2014Article
- Toll-like receptor 9 is required for chronic stress-induced immune suppression.Neuroimmunomodulation · 2014Article
- Glial abnormalities in substance use disorders and depression: does shared glutamatergic dysfunction contribute to comorbidity?The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2014Review
- Pharmacological characterization of LPS and opioid interactions at the toll-like receptor 4.British journal of pharmacology · 2013Article
- Opioid activation of toll-like receptor 4 contributes to drug reinforcement.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Mechanism(s) involved in opioid drug abuse modulation of HAND.Current HIV research · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage.
Indexed as
Identifiers
What OpenQuestion holds
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.