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dc.contributor.authorCunningham, Colmen
dc.contributor.authorMitchell, Kevinen
dc.date.accessioned2022-03-22T10:56:12Z
dc.date.available2022-03-22T10:56:12Z
dc.date.issued2021en
dc.date.submitted2021en
dc.identifier.citationMcGarry, N. and Murray, C.L. and Garvey, S. and Wilkinson, A. and Tortorelli, L. and Ryan, L. and Hayden, L. and Healy, D. and Griffin, E.W. and Hennessy, E. and Arumugam, M. and Skelly, D.T. and Mitchell, K.J. and Cunningham, C., Double stranded RNA drives anti-viral innate immune responses, sickness behavior and cognitive dysfunction dependent on dsRNA length, IFNAR1 expression and age, Brain, Behavior, and Immunity, 95, 2021, 413-428en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/98339
dc.descriptionPUBLISHEDen
dc.descriptioncited By 4en
dc.description.abstractDouble 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.en
dc.format.extent413-428en
dc.language.isoenen
dc.relation.ispartofseriesBrain, Behavior, and Immunityen
dc.relation.ispartofseries95en
dc.rightsYen
dc.subjectDouble stranded RNAen
dc.subjectviral replicationen
dc.subjectAlzheimer’s diseaseen
dc.subjectIL-6en
dc.subjectTNF-αen
dc.subjectSARS-CoV-2en
dc.subjectCOVID19en
dc.subjectAgeen
dc.subjectCytokinesen
dc.subjectNeuroinflammationen
dc.subjectSickness behaviouren
dc.subjectCNSen
dc.subjectSystemic inflammationen
dc.subjecttype I interferonen
dc.subjectdsRNAen
dc.subjectPoly I:Cen
dc.titleDouble stranded RNA drives anti-viral innate immune responses, sickness behavior and cognitive dysfunction dependent on dsRNA length, IFNAR1 expression and ageen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/cunnincoen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kemitcheen
dc.identifier.rssinternalid239701en
dc.identifier.doihttp://dx.doi.org/10.1016/j.bbi.2021.04.016en
dc.rights.ecaccessrightsopenAccess
dc.identifier.orcid_id0000-0003-1423-5209en


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