Objective: To explore the underlying mechanisms of the association between periodontitis and cognitive impairment.

Methods: Single-nucleus transcriptomics of mice were used to investigate the impact of periodontitis on brain and hippocampal cells to gain insights into disease progression. After data processing, functional enrichment, pathway analysis and cell-cell communication analysis were used to identify the distinct pathways and genes upregulated in Alzheimer's disease (AD) linked to periodontitis. After cell culture, real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to confirm the results.

Results: The present authors identified endothelial inflammation as a key factor in periodontitis-related AD. The findings revealed that the upregulation of Mgll expression in endothelial cells was linked to increased antigen presentation and exacerbated neuroinflammation, potentially worsening AD. Moreover, the present authors elucidated MGLL-2AG-CB2 signalling, through which MGLL activation suppresses CB2 expression and leads to heightened inflammation, while MGLL inhibition restores CB2 levels and mitigates inflammation.

Conclusion: The present study revealed the role of MGLL in linking periodontitis to hippocampal endothelial inflammation and antigen presentation in cognitive impairment. This research will enhance the understanding of how periodontitis impacts cognition and explore potential therapeutic strategies to alleviate periodontitis-associated cognitive impairment.

Keywords: MGLL; cognitive impairment; endothelial inflammation; periodontitis; single-nucleus transcriptomics.

目标：

探索牙周炎与认知障碍之间关联的潜在机制。

方法：

采用单核转录组学技术研究小鼠脑和海马细胞在牙周炎影响下的变化，以深入了解疾病进展。经过数据处理后，使用功能富集分析、通路分析及细胞间通讯分析来识别与牙周炎相关的阿尔茨海默病（AD）中上调的特异性途径和基因。在细胞培养之后，采用实时定量聚合酶链反应（RT-qPCR）和酶联免疫吸附测定（ELISA）验证实验结果。

结果：

当前研究发现内皮炎症是牙周炎相关阿尔茨海默病的关键因素。研究表明，在内皮细胞中Mgll表达的上调与抗原呈递增加及神经炎症加剧有关，可能使AD恶化。此外，目前的研究阐明了MGLL-2AG-CB2信号通路，通过该通路发现MGLL激活抑制CB2表达并导致炎症水平升高，而MGLL抑制则恢复CB2水平并减轻炎症。

结论：

本研究揭示了MGLL在连接牙周炎与海马内皮炎症及抗原呈现在认知障碍中的作用。这项研究将加深对牙周炎影响认知的理解，并探索潜在的治疗策略以缓解牙周炎相关的认知障碍。

关键词：

MGLL；认知障碍；内皮炎症；牙周炎；单核转录组学。