Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice
Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice
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DOI：
10.1016/j.expneurol.2020.113176
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发表时间：
2020-01
影响因子：
5.3
通讯作者：
Li Xue;Xiaojun Zou;Xueqin Yang;Fu Peng;Dong-ke Yu;Jun-Rong Du
中科院分区：
文献类型：
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作者：
Li Xue;Xiaojun Zou;Xueqin Yang;Fu Peng;Dong-ke Yu;Jun-Rong Du
流行病学研究表明，慢性牙周炎（CP）与认知功能障碍的发生和发展密切相关。本研究探讨了CP与小鼠认知能力下降之间的因果关系及其机制。长期结扎左侧上颌第二磨牙周围的牙齿被用来诱导小鼠CP。在12个月的时间内，在牙龈组织中观察到严重的牙槽骨丢失和炎症变化，并伴有进行性认知障碍。我们还观察到大脑神经元和突触损伤和胶质细胞活化在这个小鼠模型的CP。此外，CP小鼠表现出口腔和肠道微生物群的显著失调，肠屏障和血脑屏障的破坏，促炎细胞因子和脂多糖（LPS）的血清含量增加，以及脑LPS水平、Toll样受体4（TLR 4）表达、核因子-κB（NF-κB）核转位和促炎细胞因子mRNA水平增加。提示CP可直接导致小鼠进行性认知功能下降，其机制可能与微生物群-肠-脑轴紊乱、LPS/TLR 4/NF-κB信号通路激活及神经炎症反应有关。因此，微生物群-肠-脑轴可能为CP相关认知功能障碍的预防和治疗提供潜在的策略。
Epidemiological studies suggest that chronic periodontitis (CP) is closely associated with the incidence and progression of cognitive impairment. The present study investigated the causal relationship between CP and cognitive decline and the underlying mechanism in mice. Long-term ligature around the left second maxillary molar tooth was used to induce CP in mice. Severe alveolar bone loss and inflammatory changes were observed in gingival tissues, accompanied by progressive cognitive deficits during a 12-month period. We also observed cerebral neuronal and synaptic injury and glial activation in this mouse model of CP. Furthermore, CP mice exhibited significant dysbiosis of the oral and gut microbiota, disruption of the intestinal barrier and blood-brain barrier, increases in the serum contents of proinflammatory cytokines and lipopolysaccharide (LPS), and increases in brain LPS levels, Toll-like receptor 4 (TLR4) expression, nuclear factor-κB (NF-κB) nuclear translocation and proinflammatory cytokine mRNA levels. These results indicate that CP may directly induce progressive cognitive decline and its mechanism is probably related to microbiota-gut-brain axis disorders, LPS/TLR4/NF-κB signaling activation and neuroinflammatory responses in mice. Therefore, the microbiota-gut-brain axis may provide the potential strategy for the prevention and treatment of CP-associated cognitive impairment.