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.
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。