Porphyromonas gingivalis-induced periodontitis promotes neuroinflammation and neuronal loss associated with dysfunction of the brain barrier

作者：Yiting Jiang, Lina Xu, Xuri Zhao, Hui Shen, Che Qiu, Zhiyan He, Zhongchen Song, Wei Zhou · 发表于：Frontiers in Cellular and Infection Microbiology · 年份：2025 · DOI：10.3389/fcimb.2025.1559182 · 被引用次数：17 · 研究领域：Barrier Structure and Function Studies、Cerebrospinal fluid and hydrocephalus、Salivary Gland Disorders and Functions

Background In our previous study, Porphyromonas gingivalis ( P. gingivalis )-induced periodontitis caused cognitive impairment which was associated with abnormal amyloid β (Aβ) metabolite in the brain. The brain barrier is critical in maintaining homeostasis, controlling influx and efflux transport and regulating waste clearance. However, the specific role of the brain barrier in linking periodontitis to cognitive function remains unclear. Methods A murine model of periodontitis-induced cognitive impairment was constructed via oral topical application of P. gingivalis. Neuroinflammation was observed by detecting the expression of proinflammatory cytokines and glia activation. Western blot (WB), immunohistochemistry (IHC) and immunofluorescence (IF) were used to detect the expression of tau-related molecules and neuronal loss. WB, Evans blue staining and flow cytometry were used to evaluate the blood-brain barrier (BBB) function including the infiltration of P. gingivalis and immune cells, and BBB permeability. The changes of meningeal lymphatic drainage were observed using an in vivo animal imaging system and reverse transcription polymerase chain reaction (RT-PCR). The effect of P. gingivalis on lymphatic endothelial cells (LECs) was further verified using IF and RT-PCR. Results P. gingivalis -induced periodontitis exacerbated cognitive impairment by the upregulation of proinflammatory cytokine and glia activation. In the brain of periodontitis mice, p-Akt and p-GSK3β levels...