Related Experiment Video
Updated: May 6, 2026

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Alterations in Neuroinflammation, Microglia and Neuroplasticity in the Rat Hippocampus in a Combined Model of
Javier Robledo-Montaña1,2, David Martín-Hernández1,2, Javier Cuenca-Ortega1,2
1Department of Pharmacology and Toxicology, Faculty of Medicine, Complutense University of Madrid (UCM), Hospital 12 de Octubre Research Institute (Imas12), Neurochemistry Research Institute UCM (IUIN), and REIS (Network of Stress Research), Madrid, Spain.
Aims:
The exact causes of major depressive disorder (MDD) are still debated, but its connection with inflammatory diseases and stress is well established. Emerging evidence suggests a potential link between periodontitis (gum disease) and MDD.
Methods:
Periodontitis (P) was induced in rats through oral rinses with the pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum for 12 weeks, followed by 3 weeks of chronic mild stress (CMS) to induce depressive-like behavior. Four experimental groups were established: periodontitis with CMS (P + CMS+), periodontitis without CMS (P + CMS-), CMS without periodontitis (P-CMS+), and control (P-CMS-). Inflammatory and synaptic plasticity-related mediators were quantified in hippocampal samples. The number, morphology, and inflammatory phenotype of microglia were also evaluated by ultrastructural and fractal analyses.
Results:
P + CMS+ animals compared with controls showed: (1) increased protein expression of TLR-4, phospho(p)-nuclear factor kappa B (p-NFκB)/NFκB ratio, and inducible nitric oxide synthase (iNOS); (2) decreased microglial number, shorter branch length, reduced complexity, and increased expression of iNOS; (3) decreased protein levels of BDNF and synaptophysin, and lower ratios of p-protein kinase B (p-Akt)/Akt and p-mammalian target of rapamycin (p-mTOR)/mTOR.
Conclusion:
Alterations in neuroinflammation and neuroplasticity in the hippocampus may contribute to the comorbidity between periodontitis and MDD, warranting further investigation.

