ArticleBiological psychiatry2013
ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pharmacogenetic Evidence in Opioid-Related Toxicity and Death with an Appraisal of Emerging Multi-Omics Studies: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.Translational psychiatry · 2026Pooled it
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Escalated Oxycodone Self-Administration Is Associated with Activation of Specific Gene Networks in the Rat Dorsal Striatum.International journal of molecular sciences · 2025Article
- ELK1 regulates BMPR1B transcriptional activity in ovine granulosa cells.Frontiers in cell and developmental biology · 2025Article
- OPRM1 Gene Polymorphism in Women with Alcohol Use Disorder.International journal of molecular sciences · 2024Article
- Identifying novel gene dysregulation associated with opioid overdose death: A meta-analysis of differential gene expression in human prefrontal cortex.medRxiv : the preprint server for health sciences · 2024Article
- Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.Molecular psychiatry · 2023Article
- Circular RNA regulation and function in drug seeking phenotypes.Molecular and cellular neurosciences · 2023Review
- MicroRNA-mediated translational pathways are regulated in the orbitofrontal cortex and peripheral blood samples during acute abstinence from heroin self-administration.Advances in drug and alcohol research · 2023Article
- The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1.Scientific reports · 2022Article
- Differential expression ofDrug and alcohol dependence reports · 2022Article
- microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats.The European journal of neuroscience · 2022Article
- Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder.Translational psychiatry · 2022Article
- Heroin Regulates Orbitofrontal Circular RNAs.International journal of molecular sciences · 2022Article
- Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats.Journal of neuroscience research · 2022Article
- Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder.Biological psychiatry · 2021Article
- The molecular neurobiology and neuropathology of opioid use disorder.Current research in neurobiology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAbuse of heroin and prescription opiate medications has grown to disturbing levels. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders.
methodsWe examined molecular mechanisms related to MOR in postmortem human brain striatal specimens from a homogenous European Caucasian population of heroin abusers and control subjects and in an animal model of heroin self-administration. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history.
resultsA characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Striatal ELK1 in heroin abusers associated with the polymorphism rs2075572 in OPRM1 in a genotype dose-dependent manner and correlated with documented history of heroin use, an effect reproduced in an animal model that emphasizes a direct relationship between repeated heroin exposure and ELK1 dysregulation. A central role of ELK1 was evidenced by an unbiased whole transcriptome microarray that revealed ~20% of downregulated genes in human heroin abusers are ELK1 targets. Using chromatin immune precipitation, we confirmed decreased ELK1 promoter occupancy of the target gene Use1.
conclusionsELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1.
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