Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice
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BACKGROUND: Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) is one of the major pathogenic factors of chronic periodontitis (CP). Few reports on the correlation between P. gingivalis-LPS and cognitive function exist. Thus, the present study aimed to investigate the effects of P. gingivalis-LPS on cognitive function and the associated underlying mechanism in C57BL/6 mice. METHODS: ). After 7 days, behavioral alterations were assessed with the open field test (OFT), Morris water maze (MWM) test, and passive avoidance test (PAT). The activation of astrocytes and microglia in the cerebral cortex and hippocampus of mice was observed by immunohistochemistry. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), TLRs (TLR2, TLR3, and TLR4), and CD14 and the activation of the NF-κB signaling pathway (IRAK1, p65, and p-p65) in the cerebral cortex of the mice were evaluated by RT-PCR, ELISA, and western blot. RESULTS: The OFT showed that P. gingivalis-LPS did not affect the initiative and activity of mice. Administration of P. gingivalis-LPS significantly impaired spatial learning and memory during the MWM test and attenuated the ability of passive avoidance learning during the PAT. Both astrocytes and microglia were activated in the cortex and hippocampus. The messenger RNA (mRNA) and protein expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) was upregulated by P. gingivalis-LPS in the cortex. In addition, the TLR4/NF-κB signaling pathway was activated (TLR4, CD14, IRAK1, and p-p65). These effects were effectively alleviated by TAK-242. CONCLUSIONS: Administration of P. gingivalis-LPS can lead to learning and memory impairment in C57BL/6 mice. This impairment is mediated by activation of the TLR4 signaling pathway. Our study suggests that P. gingivalis-LPS-induced neuroinflammation plays an important role in cognitive impairment. It also reveals that endotoxins of periodontal pathogens could represent a risk factor for cognitive disorders.
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Chronic oral application of Porphyromonas gingivalis or injection of P. gingivalis LPS results in brain inflammation and neurodegeneration in wild-type mice.
“Chronic oral application of P. gingivalis or injection of P. gingivalis LPS results in brain inflammation and neurodegeneration in wild-type mice [70, 89].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [89]
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- Authors
- Zhang, J., Yu, C., Zhang, X., Chen, H., Dong, J., Lu, W., Song, Z., & Zhou, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Song, Zhongchen
- Zhou, Wei
- Venue
- Journal of Neuroinflammation
- Published
- 2018-02-09
- Volume
- 15
- Issue
- 1
- Pages
- 37-37
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC5810193
- OpenAlex
- W2802436906
- Cited by
- 297
- References
- 43
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 53 · 2023: 49 · 2022: 44 · 2021: 45 · 2020: 25 · 2019: 13 · 2018: 5
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81670992, 81273519)
- Shanghai Summit & Plateau Disciplines (20152523)
- Chinese Stomatological Association (CSAY2015-01)
- Interdisciplinary Program of Shanghai JiaoTong University (YG2015MS07, YG2015MS04)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Porphyromonas gingivalis, lipopolysaccharide, cognitive impairment, neuroinflammation, TLR4 signaling, NF-κB signaling, chronic periodontitis, spatial learning and memory, passive avoidance learning, astrocyte activation, microglial activation, inflammatory cytokines, TAK-242, periodontal pathogens, endotoxin
- MeSH terms
- Animals, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Random Allocation, Sulfonamides, Signal Transduction, Porphyromonas gingivalis, Maze Learning, Toll-Like Receptor 4, Mice, Cognitive Dysfunction
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