Chronic low-grade hippocampal inflammation blunts exercise-induced neurogenesis and alters the exercise-induced microglia transcriptome in the rat hippocampus
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Date
2026-05-29
Authors
Nicolas, Sarah
Caruso, Maria Giovanna
Dohm-Hansen, Sebastian
Foley, Tara
Lucassen, Paul J
Mul, Joram D
Lavelle, Aonghus
English, Jane E
O'Leary, Olivia F
Nolan, Yvonne M
Journal Title
Journal ISSN
Volume Title
Publisher
Academic Press Inc.
Published Version
Abstract
Chronic 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. We assessed effects on multiple dorsal hippocampal-related behaviours, adult hippocampal neurogenesis, microglial reactivity, 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.
Description
Keywords
Behaviour , Chronic neuro inflammation , Exercise , Hippo campal neurogenesis , Hippocampus , IL-1β , Microglia , [Medicine] , Chronic Neuro inflammation
Citation
Nicolas, 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