ArticleProceedings of the National Academy of Sciences of the United States of America2019
Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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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
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues.Annual review of biomedical engineering · 2021Pooled it
- Interferon-mediated regulation of the neurovascular unit in diabetic retinopathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Cytokine-mediated immune-to-brain signaling in neural circuit disorders.Experimental & molecular medicine · 2026Review
- TNF-α and IFN-γ impair neural oscillations and induce neurodegeneration by microglial nitric oxide, metabolic and oxidative stress.Journal of neuroinflammation · 2026Article
- γδ T Cell-Mediated Neuroimmune Interactions in Skin Inflammation and Allergy.Clinical reviews in allergy & immunology · 2026Review
- Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.Science advances · 2026Article
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- T cell-microglial interactions that impair myelin maintenance and regeneration: cellular mechanisms on white-matter associated changes.Frontiers in immunology · 2026Review
- Natural killer T cells in intracerebral hemorrhage: phase-dependent immune responses and therapeutic implications.Frontiers in immunology · 2026Review
- Identification of plasma inflammatory biomarkers for Alzheimer's disease reveals IFN-γ as a regulator of ACSL1-mediated microglia phenotype.Frontiers in immunology · 2026Article
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Timed microglia depletion promotes functional network reorganization and motor recovery after stroke.Brain communications · 2026Article
- Review
- High-throughput cytokine detection platform for evaluation of chemical induced microglial activation.SLAS technology · 2025Article
- Gamma Oscillation Disruption Induced By Microglial Activation Contributes to Perioperative Neurocognitive Disorders in Aged Mice.Journal of molecular neuroscience : MN · 2025Article
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Loss of insulin signaling in microglia impairs cellular uptake of Aβ and neuroinflammatory response exacerbating AD-like neuropathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CSF cytokine, chemokine and injury biomarker profile of glial fibrillary acidic protein (GFAP) autoimmunity.Annals of clinical and translational neurology · 2025Article
- Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type II IFN (IFN-γ) is a proinflammatory T lymphocyte cytokine that serves in priming of microglia-resident CNS macrophages-during the complex microglial activation process under pathological conditions. Priming generally permits an exaggerated microglial response to a secondary inflammatory stimulus. The impact of primed microglia on physiological neuronal function in intact cortical tissue (in situ) is widely unknown, however. We explored the effects of chronic IFN-γ exposure on microglia in hippocampal slice cultures, i.e., postnatal parenchyma lacking leukocyte infiltration (adaptive immunity). We focused on fast neuronal network waves in the gamma-band (30-70 Hz). Such gamma oscillations are fundamental to higher brain functions, such as perception, attention, and memory, and are exquisitely sensitive to metabolic and oxidative stress. IFN-γ induced substantial morphological changes and cell population expansion in microglia as well as moderate up-regulation of activation markers, MHC-II, CD86, IL-6, and inducible nitric oxide synthase (iNOS), but not TNF-α. Cytoarchitecture and morphology of pyramidal neurons and parvalbumin-positive inhibitory interneurons were well-preserved. Notably, gamma oscillations showed a specific decline in frequency of up to 8 Hz, which was not mimicked by IFN-α or IL-17 exposure. The rhythm disturbance was caused by moderate microglial nitric oxide (NO) release demonstrated by pharmacological microglia depletion and iNOS inhibition. In conclusion, IFN-γ priming induces substantial proliferation and moderate activation of microglia that is capable of slowing neural information processing. This mechanism might contribute to cognitive impairment in chronic brain disease featuring elevated IFN-γ levels, blood-brain barrier leakage, and/or T cell infiltration, well before neurodegeneration occurs.
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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.