npj Aging ( IF 4.1 ) Pub Date : 2017-11-06 , DOI: 10.1038/s41514-017-0015-x
Naoyuki Ishida , Yuichi Ishihara , Kazuto Ishida , Hiroyuki Tada , Yoshiko Funaki-Kato , Makoto Hagiwara , Taslima Ferdous , Mohammad Abdullah , Akio Mitani , Makoto Michikawa , Kenji Matsushita
![]() |
Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer’s disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis-inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.
中文翻译:

细菌感染引起的牙周炎加剧了转基因小鼠的阿尔茨海默氏病特征
牙周炎是一种由牙周病细菌引起的局部感染性疾病,例如牙龈卟啉单胞菌。近来,已经提出细菌感染可能有助于阿尔茨海默氏病(AD)的发作和发展。但是,我们没有任何证据表明牙周炎与AD之间存在因果关系。在这项研究中,我们通过使用AD的转基因小鼠模型调查了牙龈卟啉单胞菌是否诱发了牙周炎调节AD的病理特征。与对照组APP-Tg小鼠相比,牙周炎诱导的APP-Tg小鼠的认知功能明显受损。接种的APP-Tg小鼠的海马和皮质中Amiloidβ(Aβ)沉积,Aβ40和Aβ42的水平均高于对照APP-Tg小鼠。此外,接种小鼠的大脑中IL-1β和TNF-α的水平高于对照小鼠。牙龈假单胞菌接种的小鼠的血清和脑中LPS的水平增加。牙龈卟啉单胞菌LPS诱导神经细胞培养物中Aβ40和Aβ42的产生,并在以Aβ引发的小胶质细胞培养物中强烈增强TNF-α和IL-1β的产生。牙龈卟啉单胞菌诱发的牙周炎 通过涉及触发脑部炎症的机制,可能加剧脑Aβ沉积,导致认知障碍增强。