ArticleThe Journal of biological chemistry2010
Morphine modulation of thrombospondin levels in astrocytes and its implications for neurite outgrowth and synapse formation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- Hippocampal Development in a Rat Model of Perigestational Opioid Exposure.bioRxiv : the preprint server for biology · 2026Article
- Article
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure.Cells · 2024Article
- Astrocytic transcriptional and epigenetic mechanisms of drug addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Article
- Methadone alters transcriptional programs associated with synapse formation in human cortical organoids.Translational psychiatry · 2023Article
- Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.Molecular psychiatry · 2023Article
- The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.Current issues in molecular biology · 2022Review
- Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake.Translational psychiatry · 2022Article
- Effects of cyanocobalamin and its combination with morphine on neuropathic rats and the relationship between these effects and thrombospondin-4 expression.The Korean journal of pain · 2022Article
- Astrocytes in Addictive Disorders.Advances in neurobiology · 2021Article
- Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure.Frontiers in pediatrics · 2021Article
- Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder.Nature communications · 2020Article
- Interaction of opioid with insulin/IGFs signaling in Alzheimer's disease.Journal of molecular neuroscience : MN · 2020Review
- Morphine promotes neovascularizing retinopathy in sickle transgeneic mice.Blood advances · 2019Article
- Implications of Chronic Opioid Therapy on Perioperative Complications and Long-Term Surgical Recovery.Translational perioperative and pain medicine · 2019Article
- Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis.Molecular neurobiology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Opioid receptor signaling via EGF receptor (EGFR) transactivation and ERK/MAPK phosphorylation initiates diverse cellular responses that are cell type-dependent. In astrocytes, multiple μ opioid receptor-mediated mechanisms of ERK activation exist that are temporally distinctive and feature different outcomes. Upon discovering that chronic opiate treatment of rats down-regulates thrombospondin 1 (TSP1) expression in the nucleus accumbens and cortex, we investigated the mechanism of action of this modulation in astrocytes. TSP1 is synthesized in astrocytes and is released into the extracellular matrix where it is known to play a role in synapse formation and neurite outgrowth. Acute morphine (hours) reduced TSP1 levels in astrocytes. Chronic (days) opioids repressed TSP1 gene expression and reduced its protein levels by μ opioid receptor and ERK-dependent mechanisms in astrocytes. Morphine also depleted TSP1 levels stimulated by TGFβ1 and abolished ERK activation induced by this factor. Chronic morphine treatment of astrocyte-neuron co-cultures reduced neurite outgrowth and synapse formation. Therefore, inhibitory actions of morphine were detected after both acute and chronic treatments. An acute mechanism of morphine signaling to ERK that entails depletion of TSP1 levels was suggested by inhibition of morphine activation of ERK by a function-blocking TSP1 antibody. This raises the novel possibility that acute morphine uses TSP1 as a source of EGF-like ligands to activate EGFR. Chronic morphine inhibition of TSP1 is reminiscent of the negative effect of μ opioids on EGFR-induced astrocyte proliferation via a phospho-ERK feedback inhibition mechanism. Both of these variations of classical EGFR transactivation may enable opiates to diminish neurite outgrowth and synapse formation.
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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.