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Updated: Aug 24, 2025
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
Porphyromonas gingivalis outer membrane vesicles in cerebral ventricles activate microglia in mice
Kayo Yoshida1, Kaya Yoshida2, Mariko Seyama1
1Department of Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
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.
Insights
Porphyromonas gingivalis outer membrane vesicles reach the brain, activating microglia and increasing tau pathology. This suggests a link between periodontal disease and Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Porphyromonas gingivalis (Pg) is implicated in Alzheimer's disease (AD) progression.
- The mechanism by which Pg affects brain pathology remains unclear.
Purpose of the Study:
- To investigate if Pg outer membrane vesicles (OMVs) translocate to the brain.
- To determine if Pg OMVs induce Alzheimer's disease (AD) neuropathology.
Main Methods:
- Pg OMVs were administered to mice for 12 weeks.
- OMV translocation and gingipain presence in the brain were assessed via immunohistochemistry.
- Tau protein levels, microglial activation, and inflammatory gene expression were analyzed.
Main Results:
- Gingipains were detected in mouse brain ventricles and surrounding tissues.
- Pg OMVs increased tau protein and phosphorylated tau.
- Microglial activation and pro-inflammatory cytokine gene expression were observed in a gingipain-dependent manner.
Conclusions:
- Pg OMVs can reach the brain's cerebral ventricle.
- Pg OMVs induce neuroinflammation by activating microglia.
- Periodontal disease may contribute to neurodegeneration in conditions like AD.
