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
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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 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.
Description
© 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/ ).
Keywords
Behaviour , Chronic neuro inflammation , Exercise , Hippo campal neurogenesis , Hippocampus , IL-1β , Microglia , [Medicine]
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
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