ObjectiveThis study investigated the spinal changes in ligature‐induced periodontitis and the role of periodontitis in cognitive impairment.MethodsTwenty mice were randomized into the control and chronic periodontitis (CP) groups, with the latter receiving ligature‐induced periodontitis. Cognitive performance was assessed by fear conditioning test. Periodontal inflammation and alveolar bone resorption were evaluated by micro‐computed tomography and histopathology. The hippocampal microglial activation was evaluated by immunohistochemistry (IHC). The expressions of hippocampal cytokines (TNF‐α, iNOS, IL‐1β, IL‐4, IL‐10, and TREM2) were measured by reverse transcription–polymerase chain reaction. The morphology and density of the dendritic spines were determined by Golgi–Cox staining.ResultsThe CP mice reported significant inflammatory cell infiltration and alveolar bone resorption, with marked increases in cytokine levels (TNF‐α, iNOS, IL‐1β, and TREM2) in the brain. Moreover, the CP mice showed significantly reduced freezing to the conditioned stimulus in the cued and contextual tests, indicating impaired memory. Further analyses revealed, in the hippocampus of the CP mice, enhanced microglial activation, decreased dendritic spine density, and increased proportion of thin dendritic spines.ConclusionsPeriodontitis‐induced neuroinflammation may impair the cognitive function by activating hippocampal microglia and inducing dendritic spine immaturity.

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