ArticleJournal of neuroinflammation2012
Histamine modulates microglia function.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Altered expression of histamine signaling genes in autism spectrum disorder.Translational psychiatry · 2017Pooled it
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Microglial Histaminergic Signaling Promotes Interleukin-10 Production and Ameliorates Motor Dysfunction in Parkinson's Disease.Aging and disease · 2025Article
- Neuroinflammation and pathways that contribute to tourette syndrome.Italian journal of pediatrics · 2025Review
- Histamine Modulation of the Basal Ganglia Circuitry in the Motor Symptoms of Parkinson's Disease.CNS neuroscience & therapeutics · 2025Review
- Inflammation and DNA methylation in Alzheimer's disease: mechanisms of epigenetic remodelling by immune cell oxidants in the ageing brain.Redox report : communications in free radical research · 2024Review
- Histamine stimulates human microglia to alter cellular prion protein expression via the HRH2 histamine receptor.Scientific reports · 2024Article
- Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Tuning neural circuits and behaviors by microglia in the adult brain.Trends in neurosciences · 2024Review
- An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer's brains.Immunity · 2024Article
- Histaminergic System and Vestibular Function in Normal and Pathological Conditions.Current neuropharmacology · 2024Review
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Role and mechanisms of mast cells in brain disorders.Frontiers in immunology · 2024Review
- Tackling Neuroinflammation in Cognitive Disorders with Single-targeted and Multi-targeted Histamine H3 Receptor Modulators.Current topics in medicinal chemistry · 2024Review
- Trisubstituted 1,3,5-Triazines as Histamine HMolecules (Basel, Switzerland) · 2023Article
- The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms.Current research in pharmacology and drug discovery · 2023Review
- Article
- Role of histidine decarboxylase gene in the pathogenesis of Tourette syndrome.Brain and behavior · 2022Review
- Neuronal Glial Crosstalk: Specific and Shared Mechanisms in Alzheimer's Disease.Brain sciences · 2022Review
- Histamine in the Crosstalk Between Innate Immune Cells and Neurons: Relevance for Brain Homeostasis and Disease.Current topics in behavioral neurosciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistamine is commonly acknowledged as an inflammatory mediator in peripheral tissues, leaving its role in brain immune responses scarcely studied. Therefore, our aim was to uncover the cellular and molecular mechanisms elicited by this molecule and its receptors in microglia-induced inflammation by evaluating cell migration and inflammatory mediator release.
methodsFirstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR analysis, immunocytochemistry and Western blotting. Then, we evaluated the role of histamine in microglial cell motility by performing scratch wound assays. Results were further confirmed using murine cortex explants. Finally, interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by ELISA measurements to determine the role of histamine on the release of these inflammatory mediators.
resultsAfter 12 h of treatment, 100 μM histamine and 10 μg/ml histamine-loaded poly (lactic-co-glycolic acid) microparticles significantly stimulated microglia motility via H4R activation. In addition, migration involves α5β1 integrins, and p38 and Akt signaling pathways. Migration of microglial cells was also enhanced in the presence of lipopolysaccharide (LPS, 100 ng/ml), used as a positive control. Importantly, histamine inhibited LPS-stimulated migration via H4R activation. Histamine or H4R agonist also inhibited LPS-induced IL-1β release in both N9 microglia cell line and hippocampal organotypic slice cultures.
conclusionsTo our knowledge, we are the first to show a dual role of histamine in the modulation of microglial inflammatory responses. Altogether, our data suggest that histamine per se triggers microglia motility, whereas histamine impedes LPS-induced microglia migration and IL-1β release. This last datum assigns a new putative anti-inflammatory role for histamine, acting via H4R to restrain exacerbated microglial responses under inflammatory challenge, which could have strong repercussions in the treatment of CNS disorders accompanied by microglia-derived inflammation.
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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.