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Mice study unravels the role of T. denticola in Alzheimer’s disease pathogenesis



Tau hyperphosphorylation is the key characteristic pathological hallmarks of Alzheimer’s disease (AD). Recently studies showed periodontitis and periodontal pathogen are significant risk factors for AD. Treponema denticola (T. denticola), as the main periodontal pathogen of periodontitis, has been reported a possible link with AD, however, the role of T. denticola in AD pathogenesis is still unclear.

In this study, twenty 8-week-old male C57BL/6 mice were orally administered T. denticola for 24 weeks. T. denticola DNA in the hippocampi of mice was determined by PCR. The levels and localization of tau phosphorylated at Thr181, Thr231 and Ser396 were examined by western blotting and immunohistochemistry. The activation of microglia and the levels of IL-1β and TNF-α were respectively detected by immunohistochemistry and ELISA. BV2 cells were co-cultured with T. denticola, then, the activation of BV2 cells was evaluated by immunofluorescence and the expression levels of IL-1β, TNF-α in BV2 cells were measured by qRT-PCR and ELISA. The supernatant from BV2 cells simulated by T. denticola was used to stimulated N2a cells, the levels of hyperphosphorylated tau protein at Thr181, Thr231 and Ser396 in N2a cells were detected by western blotting.

Orally administered T. denticola colonized the brain tissue, promoted the hyperphosphorylation of tau protein at Ser396, Thr181 and Thr231 in the processes of neurons, activated the microglia and increased the levels of IL-1β and TNF-α in the hippocampi of mice. In vitro, T. denticola directly induced the BV2 cells activation and increased the expression levels of IL-1β and TNF-α. Furthermore, the levels of hyperphosphorylated tau protein at Thr181, Thr231 and Ser396 in N2a cells were increased. This study found T. denticola could invade the hippocampi of mice and promote the hyperphosphorylation of tau protein at Ser396, Thr181 and Thr231 by activating the neuroinflammation in the hippocampi of mice.



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