Chronic periodontitis induces cognitive decline in young adult mice

This study investigated whether chronic periodontitis induces cognitive impairment in young adult mice and examined the mechanisms underlying periodontitis-associated cognitive decline.

Chronic periodontitis was induced in 4-month-old female C57BL/6N mice by bilateral ligature placement around the maxillary molars. Learning and memory were assessed using the Morris water maze (MWM) and novel object recognition tests at 4 and 8 weeks after ligation. At 2 and 12 weeks post-ligation, tissues from the brain, including the hippocampus and prefrontal cortex, as well as the trigeminal ganglion, gingiva, palate, and maxilla, were harvested. Alveolar bone loss and periodontal tissue destruction were evaluated using micro-computed tomography and histology, respectively. Neuroinflammatory markers, including glial fibrillary acidic protein (GFAP), tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and synapse-related gene expression, including glutamate ionotropic AMPA-type subunit 2 (Gria2), glutamate ionotropic NMDA-type subunit 2A (Grin2a), and semaphorin 4D (Sema4d), were quantified using immunofluorescence and reverse transcription quantitative polymerase chain reaction.

Ligature placement resulted in significant alveolar bone loss and periodontal tissue destruction. Early neuroinflammatory changes were evident, including increased expression levels of GFAP in the molecular layer of the dentate gyrus, GFAP in the hippocampus, and IL-6 in the trigeminal ganglion. Behavioral assessments revealed hippocampus-dependent cognitive impairment: at 4 weeks, spatial memory deficits were observed in the MWM; at 8 weeks, increased anxiety-like behavior, impaired recognition memory, and delayed spatial learning were observed. Gene expression analysis demonstrated dysregulation of synapse-related genes, including increased IL-1β and decreased Gria2 expression in the prefrontal cortex and reduced Gria2, Grin2a, and Sema4d expression in the hippocampus.

Ligature-induced chronic periodontitis in young adult mice caused alveolar bone loss and was associated with neuroinflammation, cognitive deficits, and dysregulated synaptic gene expression. These findings suggest that periodontal disease may contribute to cognitive decline through neuroinflammatory and synaptic mechanisms in younger individuals.