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. 2023 May;50(5):642-656.
doi: 10.1111/jcpe.13780. Epub 2023 Jan 27.

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  1   2 , María Martínez  3   4 , Javier Robledo-Montaña  1   2 , Marina Muñoz-López  1   2 , Leire Virto  3   5 , Nagore Ambrosio  3   4 , Maria José Marín  3 , Eduardo Montero  3   4 , David Herrera  3   4 , Mariano Sanz  3   4 , Juan C Leza  1   2 , Elena Figuero  3   4 , Borja García-Bueno  1   2
Affiliations

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 et al. J Clin Periodontol. 2023 May.

Abstract

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.

Keywords: animal model; blood-brain barrier; depression; neuroinflammation; periodontitis.

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