Periodontitis Induced by P. gingivalis-LPS Is Associated With Neuroinflammation and Learning and Memory Impairment in Sprague-Dawley Rats.

Xinyi Xia,Yi Hu,Zhongchen Song,Huiwen Chen,Wei Zhou,Jing Zhang,Xu Zhang,Huxiao Li,Che Qiu,Yue Liao

doi:10.3389/fnins.2020.00658

Abstract

BackgroundPeriodontitis is one of the most common oral diseases and is a potential risk factor for systemic diseases. In this study, we aimed to investigate the association between periodontitis and learning and memory impairment.MethodsWe established a periodontitis model by topical application of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) into the palatal gingival sulcus of the maxillary first molars of 10-week-old male rats for a 10-week period. We assessed alveolar bone resorption using micro–computed tomography analysis and learning and memory ability using the Morris water maze test. We determined the levels of cytokines [interleukin (IL)-1β, IL-6, IL-8, and IL-21] and LPS in the peripheral blood and cortex, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway activation, using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot. We determined activation of microglia and astrocytes, expression of Aβ1-42, APP and Tau by immunohistochemistry. Finally, we measured the expression of amyloid precursor protein (APP) and its key secretases, as well as the Aβ1-40/1-42 ratio, by RT-PCR, western blot, and ELISA.ResultsWe found that periodontitis induced learning and memory impairment in the rats. Further, we observed that it induced significant alveolar bone resorption. There was an increase in the levels of inflammatory cytokines and LPS. Moreover, we confirmed TLR4/NF-κB signaling pathway activation. We also observed activated microglia and astrocytes with enlarged cell bodies and irregular protrusions. Finally, we observed the promotion of β- and γ-secretases APP processing.ConclusionOur findings indicated that periodontitis was associated with learning and memory impairment, probably induced by neuroinflammation via activating the TLR4/NF-κB signaling pathway. Furthermore, abnormal APP processing could be involved in this progress.

Highlights

Periodontitis is a potentially transmissible chronic infection caused by plaque biofilm
There was a decrease in Bone volume/total volume (BV/TV) and Bone mineral density (BMD) (66.13 ± 1.98% vs. 49.56 ± 2.83% and 0.8743 ± 0.02 g/cc vs. 0.755 ± 0.02 g/cc, respectively) and an increase in BS/BV (14.92 ± 1.22/mm vs. 20.7 ± 0.40/mm) in the LPS group, which was reversed by TAK-242 (Figures 1B–D)
Compared to the LPS group, the LPS+TAK-242 group showed reduced levels of IL-1β, IL6, and IL-8 proteins (Figure 6). These findings demonstrate that periodontitis induced by P. gingivalis-LPS increases the expression of inflammatory factors in the central nervous system, which is significantly prevented by TAK-242

Summary

Introduction

Periodontitis is a potentially transmissible chronic infection caused by plaque biofilm. It is responsible for 70% of the global population presenting one or more damages in the periodontium (Oppermann et al, 2015). Given the accelerating trend of population aging, the harm caused by cognitive disorders on human health has become increasingly prominent. It clinically manifests as gradual cognitive dysfunction and psychosis (Wimo et al, 2017; Brookmeyer et al, 2018). Periodontitis is one of the most common oral diseases and is a potential risk factor for systemic diseases. We aimed to investigate the association between periodontitis and learning and memory impairment

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Conclusion