RT Journal Article
T1 Neuroinflammation related to the blood-brain barrier and sphingosine-1-phosphate in a pre-clinical model of periodontal diseases and depression in rats
A1 David Martín-Hernández, 
A1 María Martínez, 
A1 Robledo Montaña, Javier
A1 Marina Muñoz-López, 
A1 Virto Ruiz, Leire
A1 Ambrosio Elejalde, Nagore
A1 Marín Cuenda, María José
A1 Montero Solís, Eduardo
A1 Herrera González, David
A1 Sanz Alonso, Mariano
A1 Leza Cerro, Juan Carlos
A1 Figuero Ruiz, Elena
A1 García Bueno, Borja
AB AimTo 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 MethodsThis 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.ResultsCMS 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.ConclusionsMicroglia, BBB permeability, and S1P pathways could be relevant mechanisms explaining the association between periodontitis and depression.
PB Wiley
SN 0303-6979
YR 2023
FD 2023-01-27
LK https://hdl.handle.net/20.500.14352/134694
UL https://hdl.handle.net/20.500.14352/134694
LA eng
NO 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
NO Clinical RelevanceScientific 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.
DS Docta Complutense
RD 8 jun 2026