Alterations in brain metabolites in rats with experimental periodontitis: A metabolomic approach

Periodontitis (PD) is a chronic inflammatory disease with systemic effects. Emerging evidence suggests a link between periodontal inflammation and neurological changes, but the biochemical mechanisms in key brain regions, such as the hippocampus and amygdala, remain unclear. Thus, we aimed to investigate metabolite alterations in the hippocampus and amygdala of rats subjected to ligature-induced PD.

Twenty-four male Wistar rats were randomly allocated into PD and Sham groups (n = 12/group). Periodontitis was induced by placing a ligature around the mandibular first molars for 14 days. After euthanasia, histomorphometric analyses of alveolar bone loss, epithelial thickness, and inflammatory cell count were performed to confirm the effectiveness of the periodontitis induction, and the hippocampus and amygdala were subsequently collected for ¹H NMR-based metabolomic analysis. Metabolites were identified and quantified, and data were analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA).

The OPLS-DA revealed distinct metabolite profiles in both the hippocampus and amygdala of animals with periodontitis. In the hippocampus, acetate and glycerol levels were decreased, while myo-inositol and creatine levels were elevated. In the amygdala, increased concentrations of isoleucine and glycine were observed. These metabolic alterations are consistent with mechanisms related to neuroinflammation, oxidative stress, cognitive dysfunction, and anxiety-like behavior.

Ligature-induced periodontitis leads to specific metabolic disturbances in brain regions responsible for memory and emotional processing. These findings support a potential neurobiological link between periodontitis and central nervous system dysfunction.

While periodontitis has been associated with neuroinflammation and behavioral impairments, the specific metabolic changes in central nervous system structures such as the hippocampus and amygdala remain poorly understood. This study identified altered metabolite profiles in the hippocampus and amygdala of rats with ligature-induced periodontitis, involving compounds associated with neuroinflammatory pathways and behavioral dysfunctions. These findings provide novel insight into the biochemical mechanisms linking periodontal inflammation with neurological outcomes and support further investigation into periodontitis as a potential modifiable risk factor for neuropsychiatric and cognitive disorders.