The Involvement of ProBDNF-Mediated Signaling in Periodontitis Induced Depression-Like Behavior in Mice

Objectives: Increasing studies support the association of periodontitis and psychiatric disorders like depression. However, the specific mechanisms remain to be further elucidated. The present study aimed to investigate the underlying mechanism of proBDNF-mediated signaling in periodontitis induced depression in mice.
Methods: Experimental periodontitis was induced in mice by periodontal injection of lipopolysaccharide (LPS) from Porphyromonas gingivalis for 3 weeks. Control group received saline alone (n=10). Bodyweight was recorded for the entire experimental period. Gingival tissue inflammation and alveolar bone resorption were examined by H&E staining and micro-CT analysis, respectively. The sucrose preference test, tail suspension test, and forced-swim test were performed to assess the abnormality in depression-like behaviors. The activation of microglia and astrocytes in the hippocampus was further assessed by immunohistochemistry and immunofluorescence. Finally, the expression of proBDNF and its receptor was determined by western blot.
Results: We found that there was no significant differences in body weight between the periodontitis mice and the controls. In the experimental periodontitis mice, there was significant inflammatory response in the gingival tissues and alveolar bone loss as demonstrated by H&E staining and micro-CT, respectively. Furthermore, periodontitis mice exhibited the depression-like behavior such as significant reduction of sucrose preference and increase of immobility time in forced swimming test compared with the control mice. We also observed that the periodontitis can induce the activation of microglia and astrocytes in the brains. Importantly, we found that the level of proBDNF and its novel receptor, XPS, was elevated in hippocampus of the periodontitis mouse brains compared to that in the controls, implying the involvement of proBDNF-mediated signaling pathway in the periodontitis-induced depression-like behavior.
Conclusions: Our results indicate that LPS-induced periodontitis could cause depression-like behaviors in a periodontitis mouse model, and the underlying mechanism probably involve the proBDNF signaling via its novel receptor, XPS.