Treponema denticola Induces Neuronal Apoptosis by Promoting Amyloid-β Accumulation in Mice

Abstract

<b>Background:</b> Neuronal apoptosis is a major contributor to Alzheimer's disease (AD). Periodontitis is a significant risk factor for AD. The periodontal pathogens <i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> have been shown to initiate the hallmark pathologies and behavioral symptoms of AD. Studies have found that <i>T. denticola</i> 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 <i>T. denticola</i> in neuronal apoptosis remain unclear and its roles in AD pathology need further study. <b>Objective:</b> This study aimed to investigate whether oral infection with <i>T. denticola</i> induced alveolar bone loss and neuronal apoptosis in mice. <b>Methods:</b> C57BL/6 mice were orally administered with <i>T. denticola</i>, 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 <i>T. denticola</i> to verify in vivo results. <b>Results:</b> Mice infected with <i>T. denticola</i> exhibited more alveolar bone loss compared with the control mice. <i>T. denticola</i> oral infection induced neuronal apoptosis in hippocampi of mice. Consistent results of the apoptosis-associated protein expression were observed in N2a cells treated with <i>T. denticola</i> and Aβ_1-42 in vitro. However, the Aβ inhibitor reversed these results, suggesting that Aβ_1-42 mediates <i>T. denticola</i> infection-induced neuronal apoptosis. <b>Conclusions:</b> This study found that oral infected <i>T. denticola</i> caused alveolar bone loss, and induced neuronal apoptosis by promoting Aβ accumulation in mice, providing evidence for the link between periodontitis and AD.