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Oral Treponema denticola Infection Induces Aβ1–40 and Aβ1–42 Accumulation in the Hippocampus of C57BL/6 Mice

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Abstract

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aβ1–40 and Aβ1–42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1–42 and Aβ1–40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

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Data Availability

The data sets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank M.D. Jia-Jia Wang Yubin Cao and Yuan-Yuan Yin for their help with our experiments and M.M. Rui-Ting Peng for the T. denticola strain.

Funding

This work was supported by a research grant from the Sichuan Province Science and Technology Key Research and Development Program, Chengdu, China (grant no. 2018SZ0163), and the Geriatric Health Care and Medical Research Center, Sichuan University, Chengdu, Sichuan Province, China.

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Authors and Affiliations

  1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China

    Xinyi Su, Zhiqun Tang, Yuqiu Liu, Wanzhi He, Jiapei Jiang, Yifan Zhang & Hongkun Wu

  2. Department of Stomatology Beijing Hospital, Institute of Geriatric Medicine, National Center of Gerontology, Beijing, 100000, China

    Zhiyue Lu

Authors
  1. Xinyi Su
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  2. Zhiqun Tang
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  4. Yuqiu Liu
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  5. Wanzhi He
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  7. Yifan Zhang
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  8. Hongkun Wu
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Contributions

All authors contributed to the study. Hongkun Wu was responsible for conceiving, designing, and supervising the present study, and guiding the revision of the manuscript. Zhiyue Lu was responsible for manuscript revision and professional editing. Material preparation, data collection, and analysis were performed by Xinyi Su, Zhiqun Tang, Yuqiu Liu, Wanzhi He, Jiapei Jiang and Yifan Zhang. The first draft of the manuscript was written by Xinyi Su. All authors commented on previous versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Hongkun Wu.

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Research Involving Human and Animal

All animal experiments were conducted at the State Key Laboratory of Oral Diseases and were licensed by the Research Ethics Committee of West China Hospital of Stomatology (no. WCHSIRB-D2019-013).

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The authors declare that they have no competing interests.

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Su, X., Tang, Z., Lu, Z. et al. Oral Treponema denticola Infection Induces Aβ1–40 and Aβ1–42 Accumulation in the Hippocampus of C57BL/6 Mice. J Mol Neurosci 71, 1506–1514 (2021). https://doi.org/10.1007/s12031-021-01827-5

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  • DOI: https://doi.org/10.1007/s12031-021-01827-5

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