Periodontitis And Neuroinflammation: A Preclinical In-Vivo Model

Objectives: To determine whether Wistar rats with induced periodontitis present a greater neuroinflammation after exposure to chronic mild stress (CMS).
Methods: An in-vivo preclinical model in Wistar rats was developed. Periodontitis was induced by oral gavages with a solution of Porphyromonas gingivalis and Fusobacterium nucleatum during 12 weeks (phase 1), being the animals later subjected to a depression model (phase 2) by exposure to CMS. Four groups with 10 rats per group were obtained: periodontitis and depression (P+D+); periodontitis without depression (P+D-), depression without periodontitis (P-D+) and negative control (P-D-). Periodontal clinical variables (plaque index, gingival index, probing depth, and bleeding on probing) were recorded during phase 1. The expression of inflammatory mediators (TNFα, IL-1β, iNOS, m-PGES-1, p65) and corticosterone and glucocorticoid receptor (GR) levels were quantified by EIA, Western Blot and RT-PCR in brain frontal cortex samples and plasma. T-Student and ANOVA tests were used.
Results: Higher values for the clinical periodontal variables were observed in the groups with periodontitis (p<0.01). After depression, no statistical significant differences were observed when comparing periodontal variables in the groups with or without depression (P+D+ vs P+D-). The mRNA expression of the pro-inflammatory cytokines TNFα and IL-1β, pro-inflammatory enzymes iNOS and m-PGES-1, and the protein expression of p65, the pro-inflammatory subunit of the nuclear factor κB were increased in the P+D+ group. Finally, corticosterone plasma levels and GR protein expression in frontal cortex were higher in P+D+ animals compared with the rest of groups.
Conclusions: Although the exposure to CMS in rats with induced-periodontitis did not result in a worsening in clinical periodontal outcomes, those rats exposed to periodontitis and CMS showed a more activated inflammatory response in periphery and brain. Additional studies are needed to elucidate these relationship between the observed alterations in the inflammatory response and clinical periodontal outcomes.