Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
- ■ Periodontal tissue damage is linked to cognitive decline.
- ■ Impaired macrophages disrupt periodontal tissue homeostasis.
- ■ Inhibition of the NLRP3 inflammasome restores periodontal macrophage function and prevents cognitive decline.
- ■ Nanoparticle-mediated restoration of gingival macrophage function is a novel treatment for periodontitis-related cognitive decline.
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ABSTRACT
Cognitive decline has been linked to periodontitis through an undetermined pathophysiological mechanism. This study aimed to explore the mechanism underlying periodontitis-related cognitive decline and identify therapeutic strategies for this condition. Using single-nucleus RNA sequencing we found that changes in astrocyte number, gene expression, and cell‒cell communication were associated with cognitive decline in mice with periodontitis. In addition, activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was observed to decrease the phagocytic capability of macrophages and reprogram macrophages to a more proinflammatory state in the gingiva, thus aggravating periodontitis. To further investigate this finding, lipid-based nanoparticles carrying NLRP3 siRNA (NPsiNLRP3) were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages, restoring the oral microbiome and reducing periodontal inflammation. Furthermore, gingival injection of NPsiNLRP3 reduced the number of Serpina3nhigh astrocytes inthe hippocampus and prevented cognitivedecline. This study provides a functional basis for the mechanism by which the destruction of periodontal tissues can worsen cognitive decline and identifies nanoparticle-mediated restoration of gingival macrophage function as a novel treatment for periodontitis-related cognitive decline. -
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REFERENCES
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Cite this article:
Zongshan Shen, Shuhong Kuang, Yong Zhang, Jiayao Chen, Shuting Wang, Congfei Xu, Yunjia Huang, Min Zhang, Shuheng Huang, Jun Wang, ChuanJiang Zhao, Zhengmei Lin, Xuetao Shi, Bin Cheng. Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus[J]. The Innovation, 2024, 5(1). https://doi.org/10.1016/j.xinn.2023.100547
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Zongshan Shen, Shuhong Kuang, Yong Zhang, Jiayao Chen, Shuting Wang, Congfei Xu, Yunjia Huang, Min Zhang, Shuheng Huang, Jun Wang, ChuanJiang Zhao, Zhengmei Lin, Xuetao Shi, Bin Cheng. Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus[J]. The Innovation, 2024, 5(1). https://doi.org/10.1016/j.xinn.2023.100547
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Figure 1.
Disruption of periodontal tissue homoeostasis causes cognitive impairment and an increase in the astrocyte number in the hippocampus
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Figure 2.
Astrocytes in mice with periodontal tissue damage exhibit alterations that are linked to cognitive decline
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Figure 3.
Activation of NLRP3 signalling exacerbates periodontal tissue damage due to impairment of macrophage function
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Figure 4.
Injecting NPsiNLRP3 into the gingiva prevents periodontal tissue damage and associated cognitive decline
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Figure 5.
The number of Serpina3nhigh astrocytes was significantly reduced in the hippocampus of periodontitis model mice after periodontal treatment with NPsiNLRP3
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Figure 6.
Overexpression of Serpina3n in astrocytes abolishes the beneficial effects of periodontal treatment on cognitive decline in mice
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