Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus

作者：Zongshan Shen, Shuhong Kuang, Yong Zhang, Jiayao Chen, Shuting Wang, Cong‐Fei Xu, Yunjia Huang, Min Zhang, Shuheng Huang, Jun Wang, ChuanJiang Zhao, Zhengmei Lin, Xuetao Shi, Bin Cheng · 发表于：The Innovation · 年份：2023 · DOI：10.1016/j.xinn.2023.100547 · 被引用次数：22 · 研究领域：Oral microbiology and periodontitis research、Diabetes and associated disorders、Immune cells in cancer

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 (NP siNLRP3 ) were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages, restoring the oral microbiome and reducing periodontal inflammation. Furthermore, gingival injection of NP siNLRP3 reduced the number of Serpina3n high astrocytes in the hippocampus and prevented cognitive decline. 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.