2026-06-07T19:16:05Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1346942026-04-14T00:13:19Zcom_20.500.14352_14col_20.500.14352_15

Neuroinflammation related to the blood-brain barrier and sphingosine-1-phosphate in a pre-clinical model of periodontal diseases and depression in rats David Martín-Hernández María Martínez Robledo Montaña, Javier Marina Muñoz-López Virto Ruiz, Leire Ambrosio Elejalde, Nagore Marín Cuenda, María José Montero Solís, Eduardo Herrera González, David Sanz Alonso, Mariano Leza Cerro, Juan Carlos Figuero Ruiz, Elena García Bueno, Borja Clinical Relevance Scientific rationale for study: A previous pre-clinical in vivo study has shown neuroinflammation when combining experimental periodontitis and depression, as well as the presence of Fusobacterium nucleatum in the frontal cortex. However, the molecular mechanisms behind these findings need to be elucidated. Principal findings: This experimental study in rats, exposed to periodontitis and depression, has shown an increase in microglial cells, changes in the expression of key mediators involved in the regulation of blood–brain barrier (BBB) permeability, and modulation of the sphingosine-1-phosphate signalling. Practical implications: The neuroinflammation demonstrated in this experimental model might be attributable to dysfunction in the BBB, which may warrant special preventive and therapeutic measures in patients suffering from both periodontitis and depression. Aim To explore the potential mechanisms of neuroinflammation (microglia, blood–brain barrier [BBB] permeability, and the sphingosine-1-phosphate [S1P] pathways) resulting from the association between periodontitis and depression in rats. Materials and Methods This pre-clinical in vivo experimental study used Wistar rats, in which experimental periodontitis (P) was induced by using oral gavages with Porphyromonas gingivalis and Fusobacterium nucleatum. Then, a chronic mild stress (CMS) model was implemented to induce a depressive-like behaviour, resulting in four groups: P with CMS (P+CMS+), P without CMS (P+CMS−), CMS without P (P−CMS+), and control (P−CMS−). After harvesting brain samples, protein/mRNA expression analyses and fluorescence immunohistochemistry were performed in the frontal cortex (FC). Results were analysed by ANOVA. Results CMS exposure increased the number of microglia (an indicator of neuroinflammation) in the FC. In the combined model (P+CMS+), there was a decrease in the expression of tight junction proteins (zonula occludens-1 [ZO-1], occludin) and an increase in intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1) and matrix metalloproteinase 9 (MMP9), suggesting a more severe disruption of the BBB. The enzymes and receptors of S1P were also differentially regulated. Conclusions Microglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression. 2026-04-13T12:54:22Z 2026-04-13T12:54:22Z 2023-01-27 journal article Martín-Hernández D, Martínez M, Robledo-Montaña J, Muñoz-López M, Virto L, Ambrosio N, Marín MJ, Montero E, Herrera D, Sanz M, Leza JC, Figuero E, García-Bueno B. Neuroinflammation related to the blood–brain barrier and sphingosine-1-phosphate in a pre-clinical model of periodontal diseases and depression in rats. Journal of Clinical Periodontology. 2023; 50(5):642–656. https://doi.org/10.1111/jcpe.13780 0303-6979 10.1111/jcpe.13780 https://hdl.handle.net/20.500.14352/134694 1600-051X https://doi.org/10.1111/jcpe.13780Digital Object Identifier (DOI) https://onlinelibrary.wiley.com/doi/10.1111/jcpe.13780 eng Santander-University Complutense of Madrid Projects in 2017 (PR41/17-20979; principal investigator: Elena Figuero) info:eu-repo/grantAgrement/MINECO-FEDER/PD2019/109033RB-100 (investigadores principales: Juan Carlos Leza and Elena Figuero) info:eu-repo/grantAgrement/MINECO-FEDER/SAF2017/85888-R (investigator principal: Borja Garcia-Bueno) restricted access Wiley