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 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.