Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice

Abstract Several lines of evidence implicate that chronic periodontitis (CP) increases the risk of mental illnesses, such as anxiety and depression, yet, the associated molecular mechanism for this remains poorly defined. Here, it is reported that mice subjected to CP exhibited depression‐like behav...

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Main Authors: Ting Cao, Dan Tian, Si‐Ying Wang, Yue Pan, Zhi‐Xuan Xia, Wei‐Kai Chen, Shao‐Wei Yang, Qing‐Quan Zeng, Yue‐Ling Zhao, Ling Zheng, Ning Li, Zhong‐Meng Lai, Yi‐Xiao Luo, Zu‐Cheng Shen
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202406269
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author Ting Cao
Dan Tian
Si‐Ying Wang
Yue Pan
Zhi‐Xuan Xia
Wei‐Kai Chen
Shao‐Wei Yang
Qing‐Quan Zeng
Yue‐Ling Zhao
Ling Zheng
Ning Li
Zhong‐Meng Lai
Yi‐Xiao Luo
Zu‐Cheng Shen
author_facet Ting Cao
Dan Tian
Si‐Ying Wang
Yue Pan
Zhi‐Xuan Xia
Wei‐Kai Chen
Shao‐Wei Yang
Qing‐Quan Zeng
Yue‐Ling Zhao
Ling Zheng
Ning Li
Zhong‐Meng Lai
Yi‐Xiao Luo
Zu‐Cheng Shen
author_sort Ting Cao
collection DOAJ
description Abstract Several lines of evidence implicate that chronic periodontitis (CP) increases the risk of mental illnesses, such as anxiety and depression, yet, the associated molecular mechanism for this remains poorly defined. Here, it is reported that mice subjected to CP exhibited depression‐like behaviors and hippocampal memory deficits, accompanied by synapse loss and neurogenesis impairment in the hippocampus. RNA microarray analysis disclosed that albumin D‐site‐binding protein (DBP) is identified as the most prominently upregulated target gene following CP, and in vivo and in vitro immunofluorescence methods showed that DBP is preferentially expressed in microglia but not neurons or astrocytes in the hippocampus. Interestingly, it is found that the expression of DBP is significantly increased in microglia after CP, and knockdown of microglial DBP ameliorated the behavioral abnormality, as well as reversed the synapse loss and hippocampal neurogenesis damage induced by CP. Furthermore, DBP knockdown improved the CP‐induced hippocampal inflammation and microglial polarization. Collectively, these results indicate a critical role of DBP in orchestrating chronic periodontitis‐related behavioral abnormality, hippocampal synapse loss and neurogenesis deficits, in which the microglial activation may be indispensably involved.
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spelling doaj-art-bcfa56d34f0a411a84c86ce2b51126882024-12-11T16:00:49ZengWileyAdvanced Science2198-38442024-12-011146n/an/a10.1002/advs.202406269Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in MiceTing Cao0Dan Tian1Si‐Ying Wang2Yue Pan3Zhi‐Xuan Xia4Wei‐Kai Chen5Shao‐Wei Yang6Qing‐Quan Zeng7Yue‐Ling Zhao8Ling Zheng9Ning Li10Zhong‐Meng Lai11Yi‐Xiao Luo12Zu‐Cheng Shen13Department of Children's Stomatology Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment Xiamen 361003 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology, School of Basic Medicine and Life Science Hainan Medical University Haikou 571199 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaFujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaDepartment of Anesthesiology Union Hospital, Fujian Medical University Fuzhou 350001 ChinaHunan Province People's Hospital The First‐affiliated Hospital of Hunan Normal University Changsha 410002 ChinaDepartment of Pharmacology School of Pharmacy Fujian Medical University Fuzhou 350122 ChinaAbstract Several lines of evidence implicate that chronic periodontitis (CP) increases the risk of mental illnesses, such as anxiety and depression, yet, the associated molecular mechanism for this remains poorly defined. Here, it is reported that mice subjected to CP exhibited depression‐like behaviors and hippocampal memory deficits, accompanied by synapse loss and neurogenesis impairment in the hippocampus. RNA microarray analysis disclosed that albumin D‐site‐binding protein (DBP) is identified as the most prominently upregulated target gene following CP, and in vivo and in vitro immunofluorescence methods showed that DBP is preferentially expressed in microglia but not neurons or astrocytes in the hippocampus. Interestingly, it is found that the expression of DBP is significantly increased in microglia after CP, and knockdown of microglial DBP ameliorated the behavioral abnormality, as well as reversed the synapse loss and hippocampal neurogenesis damage induced by CP. Furthermore, DBP knockdown improved the CP‐induced hippocampal inflammation and microglial polarization. Collectively, these results indicate a critical role of DBP in orchestrating chronic periodontitis‐related behavioral abnormality, hippocampal synapse loss and neurogenesis deficits, in which the microglial activation may be indispensably involved.https://doi.org/10.1002/advs.202406269albumin D‐site‐binding proteinchronic periodontitisdepression‐like behaviorshippocampusmicroglia
spellingShingle Ting Cao
Dan Tian
Si‐Ying Wang
Yue Pan
Zhi‐Xuan Xia
Wei‐Kai Chen
Shao‐Wei Yang
Qing‐Quan Zeng
Yue‐Ling Zhao
Ling Zheng
Ning Li
Zhong‐Meng Lai
Yi‐Xiao Luo
Zu‐Cheng Shen
Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
Advanced Science
albumin D‐site‐binding protein
chronic periodontitis
depression‐like behaviors
hippocampus
microglia
title Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
title_full Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
title_fullStr Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
title_full_unstemmed Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
title_short Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice
title_sort microglial dbp signaling mediates behavioral abnormality induced by chronic periodontitis in mice
topic albumin D‐site‐binding protein
chronic periodontitis
depression‐like behaviors
hippocampus
microglia
url https://doi.org/10.1002/advs.202406269
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