Porphyromonas gingivalis outer membrane vesicles in cerebral ventricles activate microglia in mice

Objective Porphyromonas gingivalis (Pg) is thought to be involved in the progression of Alzheimer's disease (AD). Whether Pg or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of Pg translocat...

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Published in:Oral diseases 2023-11, Vol.29 (8), p.3688-3697
Main Authors: Yoshida, Kayo, Yoshida, Kaya, Seyama, Mariko, Hiroshima, Yuka, Mekata, Mana, Fujiwara, Natsumi, Kudo, Yasusei, Ozaki, Kazumi
Format: Article
Language:English
Subjects:
Alzheimer's disease
cerebral ventricle
Choroid plexus
Ependymal cells
Gene expression
Gingipain
Histology
Immunohistochemistry
Inflammation
Membrane vesicles
Microglia
Neurodegeneration
Neurodegenerative diseases
neuroinflammation
outer membrane vesicle
Periodontal diseases
Polymerase chain reaction
Porphyromonas gingivalis
Tau protein
Ventricle
Ventricles (cerebral)
Western blotting
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Summary:Objective Porphyromonas gingivalis (Pg) is thought to be involved in the progression of Alzheimer's disease (AD). Whether Pg or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of Pg translocate to the brain and induce the pathogenic features of AD. Material and Methods Pg OMVs were injected into the abdominal cavity of mice for 12 weeks. Pg 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. Results Gingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells in Pg OMV‐administered mice. Tau and phosphorylated Tau protein increased and microglia were activated. Pg OMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain‐dependent manner. Conclusion Pg OMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia. Pg OMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.
ISSN:1354-523X
1601-0825
DOI:10.1111/odi.14413