Abstract：
Background: Neuronal apoptosis is a major contributor to Alzheimer\'s disease (AD). Periodontitis is a significant risk factor for AD. The periodontal pathogens Porphyromonas gingivalis and Treponema denticola have been shown to initiate the hallmark pathologies and behavioral symptoms of AD. Studies have found that T. denticola infection induced Tau hyperphosphorylation and amyloid β accumulation in the hippocampi of mice. Aβ accumulation is closely associated with neuronal apoptosis. However, the roles of T. denticola in neuronal apoptosis remain unclear and its roles in AD pathology need further study. Objective: This study aimed to investigate whether oral infection with T. denticola induced alveolar bone loss and neuronal apoptosis in mice. Methods: C57BL/6 mice were orally administered with T. denticola, Micro-CT was employed to assess the alveolar bone resorption. Western blotting, quantitative PCR, and TUNEL staining were utilized to detect the apoptosis-associated changes in mouse hippocampi. N2a were co-cultured with T. denticola to verify in vivo results. Results: Mice infected with T. denticola exhibited more alveolar bone loss compared with the control mice. T. denticola oral infection induced neuronal apoptosis in hippocampi of mice. Consistent results of the apoptosis-associated protein expression were observed in N2a cells treated with T. denticola and Aβ1-42 in vitro. However, the Aβ inhibitor reversed these results, suggesting that Aβ1-42 mediates T. denticola infection-induced neuronal apoptosis. Conclusions: This study found that oral infected T. denticola caused alveolar bone loss, and induced neuronal apoptosis by promoting Aβ accumulation in mice, providing evidence for the link between periodontitis and AD.
摘要：
背景:神经元凋亡是阿尔茨海默病(AD)的主要原因。牙周炎是AD的重要危险因素。牙周病原体牙龈卟啉单胞菌和树突螺旋体已被证明可引发AD的标志性病理和行为症状。研究发现，丁香弧菌感染可诱导Tau蛋白过度磷酸化和β淀粉样蛋白在小鼠海马中的积累。Aβ积累与神经元凋亡密切相关。然而,在神经元凋亡中的作用尚不清楚，其在AD病理中的作用有待进一步研究。目的:本研究旨在探讨口腔感染隐风毛虫是否会引起小鼠牙槽骨丢失和神经元凋亡。方法：C57BL/6小鼠口服T.denticola，Micro-CT用于评估牙槽骨吸收。西方印迹,定量PCR,和TUNEL染色用于检测小鼠海马的凋亡相关变化。将N2a与隐虫共培养以验证体内结果。结果：与对照小鼠相比，感染了T.denticola的小鼠表现出更多的牙槽骨丢失。Denticola口腔感染诱导小鼠海马神经元凋亡。在体外用T.denticola和Aβ1-42处理的N2a细胞中观察到凋亡相关蛋白表达的一致结果。然而,Aβ抑制剂逆转了这些结果，提示Aβ1-42介导了T感染诱导的神经元凋亡。结论：本研究发现口腔感染的T.denticola导致牙槽骨丢失，并通过促进小鼠Aβ积累诱导神经元凋亡，为牙周炎和AD之间的联系提供证据。
