AimBlood–brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process.Materials and MethodsC57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav‐1 levels were measured. The mechanisms of Ddx3x‐induced regulation on Mfsd2a by arginine‐specific gingipain A (RgpA) in BMECs were explored.ResultsP. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up‐regulated Cav‐1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav‐1 regulatory axis was activated.ConclusionsGingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav‐1 axis.

中文翻译：

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牙龈蛋白酶可能是牙龈卟啉单胞菌损害认知和增强血脑屏障通透性的关键毒力因子之一：一项动物研究

目的血脑屏障（BBB）障碍是认知障碍的早期发现之一。我们最近发现牙龈卟啉单胞菌菌血症可导致认知障碍和血脑屏障通透性增加。本研究旨在找出该病可能的关键毒力因子。牙龈卟啉单胞菌材料和方法C57/BL6小鼠感染牙龈卟啉单胞菌或牙龈痛或牙龈卟啉单胞菌脂多糖（牙龈卟啉单胞菌LPS组）尾静脉注射，持续8周。测量小鼠认知行为的变化、海马和大脑皮层的组织病理学变化、血脑屏障通透性的变化以及Mfsd2a和Cav-1水平的变化。探讨了 BMEC 中 Ddx3x 诱导的精氨酸特异性牙龈蛋白酶 A (RgpA) 对 Mfsd2a 的调节机制。 结果牙龈卟啉单胞菌牙龈蛋白酶显着促进小鼠认知障碍、海马和大脑皮层病理改变、血脑屏障通透性增加、抑制Mfsd2a表达、上调Cav-1表达。RgpA刺激后，体外BBB模型通透性增加，Ddx3x/Mfsd2a/Cav-1调节轴被激活。结论Gingipains可能是BBB关键毒力因子之一。磷。牙龈炎通过 Ddx3x/Mfsd2a/Cav-1 轴损害认知并增强 BBB 通透性。