Abstract：
OBJECTIVE: Blood-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.
METHODS: C57/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.
RESULTS: P. 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.
CONCLUSIONS: Gingipains 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.
METHODS: C57/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.
RESULTS: P. 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.
CONCLUSIONS: Gingipains 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.
摘要：
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引起认知障碍和BBB通透性增加。本研究旨在找出参与牙龈卟啉单胞菌病理过程的可能关键毒力因子。
方法：C57/BL6小鼠感染牙龈卟啉单胞菌或牙龈疼痛或牙龈卟啉单胞菌脂多糖（P。牙龈LPS组）通过尾静脉注射8周。小鼠的认知行为发生变化，海马和大脑皮层的组织病理学变化，BBB渗透率的变化，并测量了Mfsd2a和Cav-1水平的变化。探讨了Ddx3x诱导BMEC中精氨酸特异性牙龈蛋白酶A（RgpA）对Mfsd2a的调控机制。
结果：P.牙龈和牙龈疼痛显著促进小鼠认知障碍，海马和大脑皮层的病理变化，增加BBB通透性，抑制Mfsd2a表达和上调Cav-1表达。RgpA刺激后,体外BBB模型的通透性增加，Ddx3x/Mfsd2a/Cav-1调节轴被激活。
结论：牙龈疼痛可能是牙龈卟啉单胞菌通过Ddx3x/Mfsd2a/Cav-1轴损害认知和增强BBB通透性的关键毒力因子之一。
方法：C57/BL6小鼠感染牙龈卟啉单胞菌或牙龈疼痛或牙龈卟啉单胞菌脂多糖（P。牙龈LPS组）通过尾静脉注射8周。小鼠的认知行为发生变化，海马和大脑皮层的组织病理学变化，BBB渗透率的变化，并测量了Mfsd2a和Cav-1水平的变化。探讨了Ddx3x诱导BMEC中精氨酸特异性牙龈蛋白酶A（RgpA）对Mfsd2a的调控机制。
结果：P.牙龈和牙龈疼痛显著促进小鼠认知障碍，海马和大脑皮层的病理变化，增加BBB通透性，抑制Mfsd2a表达和上调Cav-1表达。RgpA刺激后,体外BBB模型的通透性增加，Ddx3x/Mfsd2a/Cav-1调节轴被激活。
结论：牙龈疼痛可能是牙龈卟啉单胞菌通过Ddx3x/Mfsd2a/Cav-1轴损害认知和增强BBB通透性的关键毒力因子之一。
