ArticleBrain, behavior, and immunity2021
Double stranded RNA drives anti-viral innate immune responses, sickness behavior and cognitive dysfunction dependent on dsRNA length, IFNAR1 expression and age.
Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 37 citations in OpenAlex.
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- Brain-immune interactions generate pathogen-specific sickness states.bioRxiv : the preprint server for biology · 2025Article
- 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
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- TLR3 Knockdown Attenuates Pressure-Induced Neuronal Damage In Vitro.Journal of cellular and molecular medicine · 2024Article
- Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia.Cell reports. Medicine · 2024Article
- Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.EMBO molecular medicine · 2024Article
- Immune activation state modulates infant engram expression across development.Science advances · 2023Article
- Maternal Immune Activation Induces Cortical Catecholaminergic Hypofunction and Cognitive Impairments in Offspring.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice.Signal transduction and targeted therapy · 2023Article
- The role of peripheral inflammatory insults in Alzheimer's disease: a review and research roadmap.Molecular neurodegeneration · 2023Review
- Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- The DNA repair enzyme, aprataxin, plays a role in innate immune signaling.Frontiers in aging neuroscience · 2023Article
- Evolutionary Aspects of Infections: Inflammation and Sickness Behaviors.Current topics in behavioral neurosciences · 2023Article
- Cerebral dysfunctions caused by sepsis during ageing.Nature reviews. Immunology · 2022Review
- Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice.Developmental psychobiology · 2022Article
- Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness.Journal of neuroinflammation · 2022Article
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14 authors at 3 institutions in 3 countries.
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Abstract
Double stranded RNA is generated during viral replication. The synthetic analogue poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disorders including schizophrenia, autism, Parkinson's disease and Alzheimer's disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1-6 kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNF-α responses than poly I:C of < 500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFNβ nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFNβ binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1β and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length-, IFNAR1- and age-dependent effects on anti-viral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation.
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