Porphyromonas gingivalis outer membrane vesicles in cerebral ventricles activate microglia in mice.
Porphyromonas gingivalis outer membrane vesicles in cerebral ventricles activate microglia in mice.
复制标题
脑室中的牙龈卟啉单胞菌外膜囊泡激活小鼠的小胶质细胞。
DOI：
10.1111/odi.14413
复制
发表时间：
2022
期刊：
影响因子：
3.8
通讯作者：
Ozaki K.
中科院分区：
文献类型：
--
作者：
Yoshida K.;Yoshida K.;Seyama M.;Hiroshima Y.;Mekata M.;Fujiwara N.;Kudo Y.;Ozaki K.
牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）被认为参与阿尔茨海默病（Alzheimer's disease，AD）的进展。然而，它的含量是否能到达大脑并直接影响神经病理学尚不清楚。在这里，我们调查是否外膜囊泡（OMV）的Pgtranslocate到大脑，并诱导AD的致病特征。材料和方法PgOMV被注射到小鼠腹腔12周。PgOMV易位到大脑通过免疫组化检测使用抗牙龈蛋白酶抗体。采用免疫印迹和免疫组织化学方法检测小鼠脑内Tau蛋白和小胶质细胞的活化。牙龈卟啉酶对炎症的影响进行了评估，通过真实的时间聚合酶链反应，使用人类小胶质细胞HMC 3 cells.ResultsGingipains检测到在该地区周围的脑室，脉络丛，脑室室管膜细胞在PgOMV-管理的小鼠。结论PgOMVs（包括牙龈蛋白酶）可以到达脑室，通过激活小胶质细胞诱导神经炎症，PgOMVs可以为牙周病在AD等神经退行性疾病中的作用提供更好的认识。
ObjectivePorphyromonas gingivalis(Pg) is thought to be involved in the progression of Alzheimer's disease (AD). WhetherPgor its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) ofPgtranslocate to the brain and induce the pathogenic features of AD.Material and MethodsPgOMVs were injected into the abdominal cavity of mice for 12 weeks.PgOMV translocation to the brain was detected by immunohistochemistry using an anti‐gingipain antibody. Tau protein and microglial activation in the mouse brain were examined by western blotting and immunohistochemistry. The effect of gingipains on inflammation was assessed by real‐time polymerase chain reaction using human microglial HMC3 cells.ResultsGingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells inPgOMV‐administered mice. Tau and phosphorylated Tau protein increased and microglia were activated.PgOMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain‐dependent manner.ConclusionPgOMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia.PgOMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.