Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague-Dawley rats via the P38 MAPK signaling pathway

作者全名："Jin, Ru; Ning, Xiaoqiao; Liu, Xiang; Zhao, Yueyang; Ye, Guo"

作者地址："[Jin, Ru; Liu, Xiang; Ye, Guo] Chongqing Med Univ, Stomatol Hosp, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Jin, Ru; Liu, Xiang; Ye, Guo] Chongqing Med Univ, Stomatol Hosp, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Ning, Xiaoqiao] First Peoples Hosp Wanzhou, Chongqing, Peoples R China; [Zhao, Yueyang] Chongqing Med Univ, Dept Anat, Chongqing, Peoples R China"

通信作者："Ye, G (通讯作者)，Chongqing Med Univ, Stomatol Hosp, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Ye, G (通讯作者)，Chongqing Med Univ, Stomatol Hosp, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China."

来源：FRONTIERS IN CELLULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000966637000001

JCR分区：Q2

影响因子：4.2

年份：2023

卷号：17

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：cognitive impairment; periodontitis; neuroinflammation; APP processing; P38 MAPK signaling pathway

摘要："BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process. MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-alpha, IL-1 beta, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation. ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-alpha, IL-1 beta, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes. ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment."

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