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.
The C57BL/6 mice were injected with P. gingivalis-LPS (5 mg kg−1) either with or without Toll-like receptor 4 (TLR4) inhibitor (TAK-242, 5 mg kg−1). 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.
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.
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.
Hirai K, Yoshizawa H, Hasegawa H, et al. Comparison of ability of apoptosis induction by lipopolysaccharide of Porphyromonas gingivalis with Escherichia coli. Eur J Med Res. 2003;8:208–11. PubMed
Jain S, Darveau RP. Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontol. 2010;54:53–70. CrossRef
Poole S, Singhrao SK, Kesavalu L, et al. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J Alzheimers Dis. 2013;36:665–77. PubMed
Neto JDN, Almeida AACD, Oliveira JDS, et al. Antioxidant effects of nerolidol in mice hippocampus after open field test. Neurochem Res. 2013;38(9):1861–70. CrossRef
Navarro-francés CI, Arenas MC. Influence of trait anxiety on the effects of acute stress on learning and retention of the passive avoidance task in male and female mice. Behav Process. 2014;105:6–14. CrossRef
Kitchens RL, Wang P, Munford RS. Bacterial lipopolysaccharide can enter monocytes via two CD14-dependent pathways. J Immunol. 1998;161:5534–45. PubMed
- Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice
- BioMed Central