ArticleBrain, behavior, and immunity2010
Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNalpha/beta and IL-1beta responses in the diseased brain and exacerbates chronic neurodegeneration.
Article in Brain, behavior, and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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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.
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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
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Interferon-Stimulated Gene-Mediated Defense Against Prion Infection: Noncanonical Function of Oas1a.Viruses · 2026Review
- Nano Proton Scavengers Modulate Endosomal pH to Inhibit Microglial Activation and Enhance Stroke Recovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- TLR3 activation in astrocytes attenuates the nigrostriatal pathway degeneration in rodent models of Parkinson's disease.Frontiers in cellular neuroscience · 2026Article
- Corrected Version: Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.Journal of clinical & experimental immunology · 2026Article
- The neuro-immune crosstalk between periphery and central nervous system during acute immune response to virus-mimicking RNA in parrots.Royal Society open science · 2025Article
- A co-culture system to study the effects of Poly I:C-activated microglia on the differentiation of murine primary neural stem cells.In vitro cellular & developmental biology. Animal · 2025Article
- Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4.Nature communications · 2025Article
- Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials.Translational stroke research · 2025Review
- The differential impact of HNRNPA1 isoforms on gene expression and their relevance to dsRNA-mediated innate immune response.Scientific reports · 2025Article
- Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.Developmental cell · 2025Article
- Role of glia in delirium: proposed mechanisms and translational implications.Molecular psychiatry · 2025Review
- Optimizing rWTC-MBTA Vaccine Formulations, Dosing Regimens, and Cryopreservation Techniques to Enhance Anti-Metastatic Immunotherapy.International journal of molecular sciences · 2025Article
- Enhancing natural killer cell anti-tumour activity through macrophage manipulation.Frontiers in immunology · 2025Review
- Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.EMBO molecular medicine · 2024Article
- Molecular signatures in prion disease: altered death receptor pathways in a mouse model.Journal of translational medicine · 2024Article
- Gestational immune activation disrupts hypothalamic neurocircuits of maternal care behavior.Molecular psychiatry · 2024Article
- Oncoproteins E6 and E7 upregulate topoisomerase I to activate the cGAS-PD-L1 pathway in cervical cancer development.Frontiers in pharmacology · 2024Article
- The Sixth Sense: Self-nucleic acid sensing in the brain.Advances in immunology · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimer's disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become 'primed' by the underlying neurodegeneration. The impact of systemic viral insults on existing neurodegenerative disease has not been investigated. Polyinosinic:polycytidylic acid (poly I:C) is a toll-like receptor-3 (TLR3) agonist and induces type I interferons, thus mimicking inflammatory responses to systemic viral infection. In the current study we hypothesized that systemic challenge with poly I:C, during chronic neurodegenerative disease, would amplify CNS inflammation and exacerbate disease. Using the ME7 model of prion disease and systemic challenge with poly I:C (12 mg/kg i.p.) we have shown an amplified expression of IFN-alpha and beta and of the pro-inflammatory genes IL-1beta and IL-6. Similarly amplified expression of specific IFN-dependent genes confirmed that type I IFNs were secreted and active in the brain and this appeared to have anti-inflammatory consequences. However, prion-diseased animals were susceptible to heightened acute sickness behaviour and acute neurological impairments in response to poly I:C and this treatment also accelerated disease progression in diseased animals without effect in normal animals. Increased apoptosis coupled with double-stranded RNA-dependent protein kinase (PKR) and Fas transcription suggested activation of interferon-dependent, pro-apoptotic pathways in the brain of ME7+poly I:C animals. That systemic poly I:C accelerates neurodegeneration has implications for the control of systemic viral infection during chronic neurodegeneration and indicates that type I interferon responses in the brain merit further study.
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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.