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 Congfei Xu Yunjia Huang Min Zhang Shuheng Huang Jun Wang ChuanJiang Zhao Zhengmei Lin Xuetao Shi Bin Cheng 

作者机构：Hospital of StomatologyGuangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhou 510060China National Engineering Research Centre for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Engineering of Guangdong ProvinceSouth China University of TechnologyGuangzhou 510006China School of Biomedical Science and EngineeringSouth China University of TechnologyGuangzhou 510650China The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China 

出 版 物：《The Innovation》 (创新（英文）)

年 卷 期：2024年第5卷第1期

页      面：98-108页

核心收录：

学科分类：1003[医学-口腔医学] 1002[医学-临床医学] 100302[医学-口腔临床医学] 10[医学] 

基　　金：This work was supported by the National Key Research and Development Program of China(2021YFB3800800) the National Natural Science Foundation of China(82201011,32022041,U22A200521,U22A20157,81873713) the Key Research and Development Program of Guangzhou(202007020002) the Postdoctoral Foundation of China(2021M703695,2021TQ0308). 

主　　题：NLRP3 periodontal number 

摘      要：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 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.