Periodontitis Induced by P. gingivalis-LPS Is Associated With Neuroinflammation and Learning and Memory Impairment in Sprague-Dawley Rats
Periodontitis Induced by P. gingivalis-LPS Is Associated With Neuroinflammation and Learning and Memory Impairment in Sprague-Dawley Rats
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牙周炎与神经炎症及学习记忆障碍的关系
DOI：
10.3389/fnins.2020.00658
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发表时间：
2020-07-02
影响因子：
4.3
通讯作者：
Zhou, Wei
中科院分区：
文献类型：
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作者：
Hu, Yi;Li, Huxiao;Zhou, Wei
背景牙周炎是最常见的口腔疾病之一，也是全身性疾病的潜在危险因素。方法采用牙龈卟啉单胞菌脂多糖（Porphyromonasgingivalislipopolysaccharide，P. gingivalis-LPS）局部注射于10周龄雄性大鼠上颌第一磨牙腭侧龈沟内10周，建立大鼠牙周炎模型。我们用微型计算机断层扫描分析评估牙槽骨吸收，用Morris水迷宫测试评估学习记忆能力。我们使用逆转录-聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和蛋白质印迹法测定外周血和皮质中细胞因子[白细胞介素（IL）-1 β、IL-6、IL-8和IL-21]和LPS的水平，以及Toll样受体4（TLR 4）/NF-κ B信号通路的活化。我们通过免疫组织化学测定了小胶质细胞和星形胶质细胞的活化、A β 1-42、APP和Tau的表达。最后，采用RT-PCR、Western blot和ELISA方法检测牙周炎大鼠牙周组织中淀粉样前体蛋白（APP）及其关键分泌酶的表达，以及A β 1-40/1-42的比值。此外，我们观察到，它引起了显着的牙槽骨吸收。炎性细胞因子和LPS水平升高。此外，我们证实了TLR 4/NF-κ B信号通路的激活。我们还观察到活化的小胶质细胞和星形胶质细胞，细胞体增大，突起不规则。结论牙周炎与学习记忆障碍有关，其机制可能是通过激活TLR 4/NF-κ B信号通路而引起的。此外，异常的APP处理可能参与这一进程。
Background Periodontitis 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.Methods We established a periodontitis model by topical application ofPorphyromonas gingivalislipopolysaccharide (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)-1 beta, IL-6, IL-8, and IL-21] and LPS in the peripheral blood and cortex, as well as toll-like receptor 4 (TLR4)/NF-kappa B 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 A beta 1-42, APP and Tau by immunohistochemistry. Finally, we measured the expression of amyloid precursor protein (APP) and its key secretases, as well as the A beta 1-40/1-42 ratio, by RT-PCR, western blot, and ELISA.Results We 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-kappa B signaling pathway activation. We also observed activated microglia and astrocytes with enlarged cell bodies and irregular protrusions. Finally, we observed the promotion of beta- and gamma-secretases APP processing.Conclusion Our findings indicated that periodontitis was associated with learning and memory impairment, probably induced by neuroinflammation via activating the TLR4/NF-kappa B signaling pathway. Furthermore, abnormal APP processing could be involved in this progress.