Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.
Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.
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DOI：
10.1038/s41514-017-0015-x
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发表时间：
2017
影响因子：
5
通讯作者：
Matsushita K
中科院分区：
文献类型：
--
作者：
Ishida N;Ishihara Y;Ishida K;Tada H;Funaki-Kato Y;Hagiwara M;Ferdous T;Abdullah M;Mitani A;Michikawa M;Matsushita K
牙周炎是一种由牙龈卟啉单胞菌等牙周致病菌引起的局部感染性疾病。最近，有研究表明，细菌感染可能有助于阿尔茨海默病（AD）的发病和进展。然而，我们没有任何证据表明牙周炎和AD之间存在因果关系。在这项研究中，我们调查是否通过使用转基因小鼠模型AD牙周炎诱发牙龈卟啉单胞菌调制AD的病理特征。牙周炎诱导的APP-Tg小鼠的认知功能明显受损，与对照APP-Tg小鼠相比。与对照APP-Tg小鼠相比，接种APP-Tg小鼠海马和皮质中的淀粉样β（A β）沉积、A β 40和A β 42水平较高。此外，接种小鼠脑中IL-1 β和TNF-α的水平高于对照小鼠。牙龈卟啉单胞菌接种小鼠血清和脑内LPS水平升高。牙龈卟啉单胞菌LPS诱导神经细胞培养物中A β 40和A β 42的产生，并强烈增强A β致敏的小胶质细胞培养物中TNF-α和IL-1 β的产生。牙龈卟啉单胞菌引起的牙周炎可能会加剧大脑A β沉积，通过涉及触发大脑炎症的机制导致认知障碍增强。阿尔茨海默病是长寿的祸害，将消耗未来卫生预算的巨大资源。不幸的是，该疾病的发病机制仍然是一个谜，并且没有足够的治疗或预防该疾病。一个关键的优先事项是检查影响痴呆症发展的可改变的风险因素。牙周病原体/牙周病与AD之间存在危险因素关系。在感染牙龈卟啉单胞菌（一种牙周病细菌）的阿尔茨海默病模型小鼠中，认知功能降低，淀粉样β肽沉积增加。此外，血清和脑中的炎性细胞因子和细菌内毒素增加。神经炎症可能是由这些炎症介质的增加引起的，并且阿尔茨海默病的病理可能会加剧。由于牙周感染是可治疗的，因此在此期间治疗牙周病可能有效延缓AD的发作或进展。
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. Alzheimer’s disease is a scourge of longevity that will drain enormous resources from health budgets in the future. Unfortunately, the pathogenesis of the disease remains an enigma and there is no adequate treatment or prophylaxis for the disease. One key priority is to examine the modifiable risk factors that influence the development of dementia. A risk factor relationship between periodontal pathogens/periodontal disease and AD exists. In Alzheimer’s model mice infected with Porphromonas gingivalis, a type of periodontopathic bacterium, cognitive function was reduced and deposition of amyloid β peptide was increased. Moreover, inflammatory cytokines and bacterial endotoxin were increased in the serum and brain. Neuroinflammation may be caused by an increase in these inflammatory mediators, and the pathology of Alzheimer’s disease may be exacerbated. Since periodontal infections are treatable, treatment of periodontal diseases during this period may be effective for delaying the onset or progression of AD.