ArticleMolecular neurobiology2014
Histamine induces upregulated expression of histamine receptors and increases release of inflammatory mediators from microglia.
Article in Molecular neurobiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Different genes may be involved in distal and local sensitization: A genome-wide gene-based association study and meta-analysis.European journal of pain (London, England) · 2022Pooled it
- Postmortem Studies of Neuroinflammation in Autism Spectrum Disorder: a Systematic Review.Molecular neurobiology · 2020Pooled it
- Altered expression of histamine signaling genes in autism spectrum disorder.Translational psychiatry · 2017Pooled it
- GPCR-Driven Muscarinic M1 and Histamine H1 Receptor Signaling Converging on the PI3K/Akt/mTOR Pathway: Functional Integration in Neuroinflammation and Myelin Repair in Multiple Sclerosis.Molecular neurobiology · 2026Review
- Review
- Histamine HPharmaceuticals (Basel, Switzerland) · 2026Article
- Bidirectional Interplay Between Microglia and Mast Cells.International journal of molecular sciences · 2025Review
- Modafinil Ameliorated Fibromyalgia Syndrome in Rats by Modulating Mast Cells and Microglia Activation Through Dopamine/Substance P/MRGPRX/Histamine and PI3K/p-Akt/NF-κB Signaling Pathways.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- 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
- Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- C-ter100 peptide derived from Vibrio vEP-45 protease acts as a pathogen-associated molecular pattern to induce inflammation and innate immunity.PLoS pathogens · 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
- Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases.Pharmacology & therapeutics · 2024Review
- Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.International journal of molecular sciences · 2024Article
- Histamine HInternational journal of molecular sciences · 2024Article
- Pharmacological intervention of behavioural traits and brain histopathology of prenatal valproic acid-induced mouse model of autism.PloS one · 2024Article
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Role and mechanisms of mast cells in brain disorders.Frontiers in immunology · 2024Review
- Histaminergic System and Vestibular Function in Normal and Pathological Conditions.Current neuropharmacology · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histamine is a potent mediator of inflammation and a regulator of innate and adaptive immune responses. However, the influence of histamine on microglia, the resident immune cells in the brain, remains uninvestigated. In the present study, we found that microglia can constitutively express all four histamine receptors (H1R, H2R, H3R, and H4R), and the expression of H1R and H4R can be selectively upregulated in primary cultured microglia in a dose-dependent manner by histamine. Histamine can also dose-dependently stimulate microglia activation and subsequently production of proinflammatory factors tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6). The antagonists of H1R and H4R but not H2R and H3R reduced histamine-induced TNF-alpha and IL-6 production, MAPK and PI3K/AKT pathway activation, and mitochondrial membrane potential loss in microglia, suggesting that the actions of histamine are via H1R and H4R. On the other hand, inhibitors of JNK, p38, or PI3K suppressed histamine-induced TNF-alpha and IL-6 release from microglia. Histamine also activated NF-kappa B and ammonium pyrrolidinedithiocarbamate, an inhibitor of NF-kappa B, and reduced histamine-induced TNF-alpha and IL-6 release. In summary, the present study identifies the expression of histamine receptors on microglia. We also demonstrate that histamine induced TNF-alpha and IL-6 release from activated microglia via H1R and H4R-MAPK and PI3K/AKT-NF-kappa B signaling pathway, which will deepen the understanding of microglia-mediated neuroinflammatory symptoms of chronic neurodegenerative disease.
Indexed as
Identifiers
What OpenQuestion holds
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.