ArticleJournal of neuroinflammation2017
Mu-opioid receptor and delta-opioid receptor differentially regulate microglial inflammatory response to control proopiomelanocortin neuronal apoptosis in the hypothalamus: effects of neonatal alcohol.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Delta-opioid receptor-mediated neural protection and regeneration.Neural regeneration research · 2026Article
- miR-146a-5p mitigates ethanol-induced neuroinflammation by targeting Btg2-dependent microglial activation.Malawi medical journal : the journal of Medical Association of Malawi · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Molecular and Cellular Mechanism of Acupuncture: Neuro-Immune Interactions Based on Endogenous Opioid System.Chinese journal of integrative medicine · 2026Review
- Application to developmental toxicity testing of a novel method for whole-brain imaging of microglia in zebrafish.Current research in toxicology · 2026Article
- Development of Delta Opioid Receptor Antagonists Which Prevent Alzheimer's Disease-Like Pathology in the 5X-Familial Alzheimer's Disease [5XFAD] Mouse Model.ACS pharmacology & translational science · 2025Article
- Formation of a β-Endorphin Corona Mitigates Alzheimer's Amyloidogenesis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Microglia Support Both the Singular Form of LTP Expressed by the Lateral Perforant Path and Episodic Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Gut Microbiome, Neuroinflammation, and Fetal Alcohol Spectrum Disorders: Insights from Rodent Models.Biology · 2025Review
- Review
- The simultaneous activation of μ- and δ-opioid receptors by (-)-2Current research in pharmacology and drug discovery · 2025Article
- Morphine-Driven m6A Epitranscriptomic Neuroadaptations in Primary Cortical Cultures.Molecular neurobiology · 2024Article
- Ethanol-activated microglial exosomes induce MCP1 signaling mediated death of stress-regulatory proopiomelanocortin neurons in the developing hypothalamus.Journal of neuroinflammation · 2024Article
- Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding.Frontiers in molecular neuroscience · 2024Review
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Review
- δ-opioid Receptor, Microglia and Neuroinflammation.Aging and disease · 2023Review
- Review
- miRNA-383 and miRNA-384 Suppress Proopiomelanocortin Gene Expression in the Hypothalamus: Effects of Early Life Ethanol Exposure.Neuroendocrinology · 2023Article
- Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia-The Role of Endocannabinoids and Microglia.International journal of molecular sciences · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOpioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus.
methodsNeonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6. Some of the alcohol-fed rats additionally received pretreatment of a microglia activation blocker minocycline. Two hours after the last feeding, some of the pups were sacrificed and processed for histochemical detection of microglial cell functions or confocal microscopy for detection of cellular physical interaction or used for gene and protein expression analysis. The rest of the pups were dissected for microglia separation by differential gradient centrifugation and characterization by measuring production of various activation markers and cytokines. In addition, primary cultures of microglial cells were prepared using hypothalamic tissues of neonatal rats and used for determination of cytokine production/secretion and apoptotic activity of neurons.
resultsIn the hypothalamus, neonatal alcohol feeding elevated cytokine receptor levels, increased the number of microglial cells with amoeboid-type circularity, enhanced POMC and microglial cell physical interaction, and decreased POMC cell numbers. Minocycline reversed these cellular effects of alcohol. Alcohol feeding also increased levels of microglia MOR protein and pro-inflammatory signaling molecules in the hypothalamus, and MOR receptor antagonist naltrexone prevented these effects of alcohol. In primary cultures of hypothalamic microglia, both MOR agonist [D-Ala 2, N-MePhe 4, Gly-ol]-enkephalin (DAMGO) and ethanol increased microglial cellular levels and secretion of pro-inflammatory cell signaling proteins. However, a DOR agonist [D-Pen2,5]enkephalin (DPDPE) increased microglial secretion of anti-inflammatory cytokines and suppressed ethanol's ability to increase microglial production of inflammatory signaling proteins and secretion of pro-inflammatory cytokines. In addition, MOR-activated inflammation promoted while DOR-suppressed inflammation inhibited the apoptotic effect of ethanol on POMC neurons.
conclusionsThese results suggest that ethanol's neurotoxic action on POMC neurons results from MOR-activated neuroinflammatory signaling. Additionally, these results identify a protective effect of a DOR agonist against the pro-inflammatory and neurotoxic action of ethanol.
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