ArticleJournal of neuroinflammation2016
Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 119 citations in OpenAlex.
- Transposable Elements Are Dynamically Regulated in Medium Spiny Neurons and May Contribute to the Molecular and Behavioral Adaptations to Cocaine.Biological psychiatry · 2026Article
- Characterize Oral-to-Blood Microbial DNA Translocation in Individuals with Cocaine Use Disorder.bioRxiv : the preprint server for biology · 2026Article
- From bugs to behavior: targeting the gut-brain interface for addiction therapeutics.Gut microbes · 2025Review
- From Stress to Substance Use Disorders: The Expanding Role of Microglia-Astrocyte Crosstalk in Neuroimmune and Glutamate Alterations in the Nucleus Accumbens.International journal of molecular sciences · 2025Review
- Regulation of glial markers expression in the rat basolateral amygdala and hippocampus during morphine aversive memory retrieval and its extinction.Behavioral and brain functions : BBF · 2025Article
- Abstinence from cocaine self-administration promotes microglial pruning of astrocytes, which drives cocaine-seeking behavior.Cell reports · 2025Article
- Protective Effects of N-Acetylcysteine in Alleviating Cocaine-Mediated Microglial Activation and Neuroinflammation.Biology · 2025Article
- Distinct circulating monocyte profiles in chronic cannabis users compared to cocaine users without changes in plasma levels of proinflammatory cytokines and LPS.NeuroImmune pharmacology and therapeutics · 2025Article
- Long noncoding RNA BCYRN1 promotes cardioprotection by enhancing human and murine regulatory T cell dynamics.The Journal of clinical investigation · 2025Article
- Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model.Translational psychiatry · 2025Article
- Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms.Frontiers in cellular neuroscience · 2025Review
- Sec10 negatively regulates antiviral immunity by downregulating NRF2-ATF4-RIG-I axis.International journal of biological sciences · 2025Article
- Cocaine-Induced Microglial Impairment and Its Rehabilitation by PLX-PAD Cell Therapy.International journal of molecular sciences · 2024Article
- NMDA receptor blockade attenuates Japanese encephalitis virus infection-induced microglia activation.Journal of neuroinflammation · 2024Article
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings.Neural regeneration research · 2024Article
- Suppression of HIV-TAT and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.Journal of neurovirology · 2024Article
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Suppression of HIV and cocaine-induced neurotoxicity and inflammation by cell penetrable itaconate esters.bioRxiv : the preprint server for biology · 2023Article
- Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Toll-like receptor 4 antagonists reduce cocaine-primed reinstatement of drug seeking.Psychopharmacology · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells.
methodsBV2 microglial cells were exposed to cocaine and assessed for toll-like receptor (TLR2) expression by quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, and immunofluorescence staining. The mRNA and protein levels of cytokines (TNFα, IL-6, MCP-1) were detected by qPCR and ELISA, respectively; level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection kit; activation of endoplasmic reticulum (ER)-stress pathways were detected by western blot. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of activating transcription factor 4 (ATF4) with the TLR2 promoter. Immunoprecipitation followed by western blotting with tyrosine antibody was used to determine phosphorylation of TLR2. Cocaine-mediated up-regulation of TLR2 expression and microglial activation was validated in cocaine-injected mice.
resultsExposure of microglial cells to cocaine resulted in increased expression of TLR2 with a concomitant induction of microglial activation. Furthermore, this effect was mediated by NADPH oxidase-mediated rapid accumulation of ROS with downstream activation of the ER-stress pathways as evidenced by the fact that cocaine exposure led to up-regulation of pPERK/peIF2α/ATF4 and TLR2. The novel role of ATF4 in the regulation of TLR2 expression was confirmed using genetic and pharmacological approaches.
conclusionsxThe current study demonstrates that cocaine-mediated activation of microglia involves up-regulation of TLR2 through the ROS-ER stress-ATF4-TLR2 axis. Understanding the mechanism(s) involved in cocaine-mediated up-regulation of ROS-ER stress/TLR2 expression and microglial activation could have implications for the development of potential therapeutic targets aimed at resolving neuroinflammation in cocaine abusers.
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