<i>Porphyromonas gingivalis</i> outer membrane vesicles in cerebral ventricles activate microglia in mice
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- Kayo Yoshida
- Department of Oral Healthcare Promotion Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Kaya Yoshida
- Department of Oral Healthcare Education Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Mariko Seyama
- Department of Oral Healthcare Promotion Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Yuka Hiroshima
- Department of Oral Microbiology Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Mana Mekata
- Department of Oral Healthcare Promotion Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Natsumi Fujiwara
- Department of Oral Healthcare Promotion Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Yasusei Kudo
- Department of Oral Bioscience Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
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- Kazumi Ozaki
- Department of Oral Healthcare Promotion Institute of Biomedical Sciences, Tokushima University Graduate School Tokushima Japan
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p><jats:italic>Porphyromonas gingivalis</jats:italic> (<jats:italic>Pg</jats:italic>) is thought to be involved in the progression of Alzheimer's disease (AD). Whether <jats:italic>Pg</jats:italic> or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of <jats:italic>Pg</jats:italic> translocate to the brain and induce the pathogenic features of AD.</jats:p></jats:sec><jats:sec><jats:title>Material and Methods</jats:title><jats:p><jats:italic>Pg</jats:italic> OMVs were injected into the abdominal cavity of mice for 12 weeks. <jats:italic>Pg</jats:italic> OMV 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Gingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells in <jats:italic>Pg</jats:italic> OMV‐administered mice. Tau and phosphorylated Tau protein increased and microglia were activated. <jats:italic>Pg</jats:italic> OMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain‐dependent manner.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p><jats:italic>Pg</jats:italic> OMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia. <jats:italic>Pg</jats:italic> OMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.</jats:p></jats:sec>
収録刊行物
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- Oral Diseases
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Oral Diseases 29 (8), 3688-3697, 2022-11-07
Wiley