Chronic low-grade hippocampal inflammation blunts exercise-induced neurogenesis and alters the exercise-induced microglia transcriptome in the rat hippocampus

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dc.contributor.authorNicolas, Sarah
dc.contributor.authorCaruso, Maria Giovanna
dc.contributor.authorDohm-Hansen, Sebastian
dc.contributor.authorFoley, Tara
dc.contributor.authorLucassen, Paul J
dc.contributor.authorMul, Joram D
dc.contributor.authorLavelle, Aonghus
dc.contributor.authorEnglish, Jane E
dc.contributor.authorO'Leary, Olivia F
dc.contributor.authorNolan, Yvonne M
dc.contributor.funderCenter for Urban Mental Health
dc.contributor.funderNederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO
dc.contributor.funderUMH
dc.contributor.funderZonMw
dc.contributor.funderNMCB
dc.contributor.funderUniversiteit van Amsterdam, UvA
dc.date.accessioned2026-07-07T12:00:02Z
dc.date.available2026-07-07T12:00:02Z
dc.date.issued2026-05-29
dc.description.abstractChronic low-grade neuroinflammation contributes to inflammageing by compromising hippocampal plasticity, with interleukin-1β (IL-1β) as a key mediator. The extent to which sustained hippocampal inflammation can interfere with the potential beneficial effects of exercise on plasticity and hippocampus-related behaviour remains unclear. Here we combined bilateral hippocampal IL-1β overexpression (IL-1β-OE), to mimic chronic low-grade neuroinflammation with voluntary wheel running, to mimic human exercise training, in adult male Sprague-Dawley rats and assessed effects on multiple dorsal hippocampal-related behaviours, adult hippocampal neurogenesis, microglial phenotype, and immune cell infiltration. Hippocampal IL-1β-OE impaired pattern separation, independent of exercise training, and attenuated exercise-induced increases in neurogenesis in the dorsal hippocampus. Hippocampal IL-1β-OE promoted microglial lipid-droplet accumulation, which exercise paradoxically exacerbated. Transcriptomic profiling revealed that exercise in combination with hippocampal IL-1β-OE, enriched immune and leukocyte trafficking pathways in microglia, while hippocampal IL-1β-OE alone increased hippocampal CD8 + T cell infiltration. These findings indicate that chronic hippocampal inflammation alters microglial and neurogenic responses to exercise, suggesting that inflammatory status critically influences exercise efficacy in supporting hippocampal plasticity.en
dc.description.sponsorshipFunding for this study was provided by Research Ireland (formerly Science Foundation Ireland) under Grant Number SFI/FFP/6820. PJL is supported by the ZonMw grant on biomedical research on ME/CFS (NMCB), by the Center for Urban Mental Health (UMH) of the University of Amsterdam, by ZonMW MODEM, by Alzheimer Nederland and by the NWO Gravitation grant ‘Institute for Chemical Neuroscience’ (iCNS).
dc.description.versionPublished Version
dc.format.extent15
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid106815
dc.identifier.authororcidNicolas, Sarah
dc.identifier.authororcidCaruso, Maria Giovanna
dc.identifier.authororcidDohm-Hansen, Sebastian
dc.identifier.authororcidFoley, Tara
dc.identifier.authororcidLucassen, Paul J
dc.identifier.authororcidMul, Joram D
dc.identifier.authororcidLavelle, Aonghus
dc.identifier.authororcidEnglish, Jane E§0000-0001-9930-7050
dc.identifier.authororcidO'Leary, Olivia F§0000-0002-9171-2032
dc.identifier.authororcidNolan, Yvonne M§0000-0003-2426-234X
dc.identifier.citationNicolas, S, Caruso, M G, Dohm-Hansen, S, Foley, T, Lucassen, P J, Mul, J D, Lavelle, A, English, J E, O'Leary, O F & Nolan, Y M 2026, 'Chronic low-grade hippocampal inflammation blunts exercise-induced neurogenesis and alters the exercise-induced microglia transcriptome in the rat hippocampus', Brain, Behavior, and Immunity, vol. 137, 106815, pp. 1-15. https://doi.org/10.1016/j.bbi.2026.106815
dc.identifier.doi10.1016/j.bbi.2026.106815
dc.identifier.endpage15
dc.identifier.issn0889-1591
dc.identifier.journaltitleBrain, Behavior, and Immunity
dc.identifier.otherORCID: /0000-0001-9930-7050/work/219992672
dc.identifier.otherORCID: /0000-0003-2426-234X/work/219992874
dc.identifier.otherORCID: /0000-0002-9171-2032/work/219993055
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19010
dc.identifier.volume137
dc.language.isoen
dc.publisherAcademic Press Inc.
dc.relation.urihttps://www.scopus.com/pages/publications/105040098917
dc.rights© 2026, the Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ).
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectBehaviour
dc.subjectChronic neuro inflammation
dc.subjectExercise
dc.subjectHippo campal neurogenesis
dc.subjectHippocampus
dc.subjectIL-1β
dc.subjectMicroglia
dc.subject[Medicine]
dc.titleChronic low-grade hippocampal inflammation blunts exercise-induced neurogenesis and alters the exercise-induced microglia transcriptome in the rat hippocampusen
dc.typeArticle (peer-reviewed)
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