Periodontal diseases and depression: A pre‐clinical in vivo study

Abstract

Aim: To analyse, through a pre-clinical in vivo model, the possible mechanisms linking depression and periodontitis at behavioural, microbiological and molecular levels.Materials and methods: Periodontitis (P) was induced in Wistar:Han rats (oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum) during 12 weeks, followed by a 3-week period of Chronic Mild Stress (CMS) induction. Four groups (n = 12 rats/group) were obtained: periodontitis and CMS (P+CMS+); periodontitis without CMS; CMS without periodontitis; and control. Periodontal clinical variables, alveolar bone levels (ABL), depressive-like behaviour, microbial counts and expression of inflammatory mediators in plasma and brain frontal cortex (FC), were measured.ANOVA tests were applied. Results:The highest values for ABL occurred in the P+CMS+ group, which also presented the highest expression of pro-inflammatory mediators (TNF-α, IL-1β and NF-kB) in frontal cortex, related to the lipoprotein APOA1-mediated transport of bacterial lipopolysaccharide to the brain and the detection of F. nucleatum in the brain parenchyma. A dysregulation of the hypothalamic-pituitary-adrenal stress axis, reflected by the increase in plasma corticosterone and glucocorticoid receptor levels in FC, was also found in this group. Conclusions:Neuroinflammation induced by F. nucleatum (through a leaky mouth) might act as the linking mechanism between periodontal diseases and depression.

Biomarkers common for inflammatory periodontal disease and depression: A systematic review

“… See appendix 3a. Martínez et al. (2021) , Spain 47: 11 controls; 12 IPD; 12 MD; 12 IPD ​+ ​MD Rats, 0% female Animals with induced periodontitis or depressive-like behavior alone or in combination Rat model of periodontitis induced by oral inoculation of P. gingivalis and F. nucleatum Experimental depression model using chronic mild stress +ve Rats with IPD and depressive-like behavior had significantly higher GI values compared to non-depressed rats.…”

“…TGF-β levels (pg/ml) in depression group (male 56 ​± ​3; female 51 ​± ​5) vs. healthy control group (male: 63 ​± ​7, female 58 ​± ​7); However, cortisol, IL-10 and TNF-α levels did not differ by depression status. Martínez et al. (2021) Corticosterone, GR receptor, LPS and 16S rRNA genes of P. gingivalis , F. nucleatum, LPS binding protein, TNF-α, IL-1β, NF-kB (p65 subunit), TLR-4, iNOS, mPGES, phosphor p38 MAPKa/b subunit, APO -A1 phospho-mTOR/mTOR ratio Plasma, frontal cortex (nuclear extract or homogenate)/ELISA, RT-PCR, Western blot Rats with depression like behavior had significantly upregulated expression of pro-inflammatory mediators (TNF-α, IL-1β, TRL-4, iNOS and p-p38) in the brain compared to controls.…”

Influence of Depression and Anxiety on Non-Surgical Periodontal Treatment Outcomes: A 6-Month Prospective Study

“…Several mechanisms have been suggested to link depression and anxiety to periodontitis. Indeed, neuroinflammation sustained by the chronic inflammation associated with periodontitis, increased systemic lipopolysaccharide and bacterial translocation from periodontal sites through a more permeable blood-brain barrier has been investigated [50,51]. The development of depression-like behavior with brain modifications was observed in mice with experimental periodontitis induced by oral gavage of Porphyromonas gingivalis, such as an increased number of activated astrocytes and decreased levels of mature brainderived neurotrophic factor and astrocytic p75NTR in the hippocampus [52].…”

Inhibitory effect of roflumilast on experimental periodontitis

“…Previous studies have shown elevated expression of NF-κB in the ligature-induced periodontitis and periimplantitis mice models, 41 and in a rat model of bacteriainduced periodontitis. 42 Lei et al demonstrated that after stroke, the activation of epinephrine induced the expression of cAMP that upregulated the level of PKA, followed by the downregulation of the level of NF-κB and weakening the proinflammatory effect of NF-κB. 43 Xu et al observed that in AlCl 3 -stimulated rat lymphocytes, the intracellular content of cAMP was increased, and the mRNA expression level of PKA was increased.…”