RT Journal Article T1 Datos manuscrito: Alterations in neuroinflammation, microglia and neuroplasticity in the rat hippocampus in a combined model of periodontitis and depression A1 Robledo Montaña, Javier A1 David Martín-Hernández, A1 Javier Cuenca-Ortega, A1 María Martínez, A1 Virto Ruiz, Leire A1 Ambrosio Elejalde, Nagore A1 Montero Solís, Eduardo A1 Marín Cuenda, María José A1 Herrera González, David A1 Sanz Alonso, Mariano A1 Leza Cerro, Juan Carlos A1 Figuero Ruiz, Elena A1 García Bueno, Borja AB 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. PB Wiley SN 1755-5930 YR 2025 FD 2025-12-01 LK https://hdl.handle.net/20.500.14352/134671 UL https://hdl.handle.net/20.500.14352/134671 LA eng NO Robledo-Montaña J, Martín-Hernández D, Cuenca-Ortega J, Martínez M, Virto L, Ambrosio N, Montero E, Marín MJ, Herrera D, Sanz M, Leza JC, Figuero E, García-Bueno B. Alterations in Neuroinflammation, Microglia and Neuroplasticity in the Rat Hippocampus in a Combined Model of Periodontitis and Depression. CNS Neurosci Ther. 2025 Dec;31(12):e70669. doi: 10.1111/cns.70669 DS Docta Complutense RD 10 jun 2026