ProBDNF signaling is involved in periodontitis-induced depression-like behavior in mouse hippocampus

Objective: Increasing evidence supports the association between periodontitis and depression. However, the specific mechanisms remain to be further elucidated. The present study aimed to mechanistically investigate the regional roles of proBDNF (the precursor of brain-derived neurotrophic factor) in periodontitis induced depression-like behavior in mice. Methods: Experimental periodontitis model was established by periodontal injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in 8-week-old male Bdnf-HA/HA mice for 3 weeks. The depression-like behaviors, spontaneous exploratory activity and the level of anxiety were assessed by behavior tests. The activation of microglia and astrocytes, as well as the expression of Interleukin (IL)-1β and Tumor necrosis factor (TNF)-α in the hippocampus, prefrontal cortex, and cortex were further assessed by immunofluorescence and western blots. The levels of IL-1β in blood serum and expression of occludin as well as claudin5 in the hippocampus, prefrontal cortex, and cortex were further determined by enzyme-linked immunosorbent assay and western blot. Finally, the expression of proBDNF, its receptors, and mature BDNF (mBDNF), as well as neuronal activity were measured by western blots and immunofluorescence. Results: Pg-LPS successfully induced periodontitis in mice and caused obvious depression-like behavior. Furthermore, we observed an increased activation of astrocytes and microglia, as well as a significant increase in expression of IL-1β and TNF-α in the hippocampus of mice treated with Pg-LPS, with elevated level of IL-1β in serum and decreased expression of occludin and claudin5 in the hippocampus. Importantly, we found that the levels of proBDNF and its receptors, SorCS2 and p75NTR, were increased significantly; however, the level of mBDNF was decreased, therefor leading to greater ratio of proBDNF/mBDNF. In addition, we also detected decreased neuronal activity in the hippocampus of mice treated with Pg-LPS. Conclusions: Our results indicate that Pg-LPS-induced periodontitis could cause depression-like behaviors in mice, and the proBDNF signaling is involved in the process.