Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, Guangdong 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, Guangdong 510055, China; The Department of Stomatology, Third Affiliated Hospital, Sun Yat-sen University, China.
Brain Behav Immun. 2019 Oct;81:523-534. doi: 10.1016/j.bbi.2019.07.012. Epub 2019 Jul 9.
Many cross-sectional epidemiological studies have shown the incidence of periodontitis is positive correlated with that of depression. However, their causal relationship and underlying mechanism are largely unknown. Porphyromonas gingivalis (Pg) is the main pathogen for periodontitis. Employing female mice treated with Pg every other day for 4 weeks, we found that Pg-mice showed obvious depression-like behavior, an increased number of activated astrocytes and decreased levels of mature brain derived neurotrophic factor (BDNF) and astrocytic p75NTR in the hippocampus. Both hippocampal injection of BDNF and overexpression of p75NTR in astrocytes alleviated Pg-induced depression-like behavior in mice. Moreover, Pg-lipopolysaccharides (LPS) generated similar phenotypes, which were reversed by the TLR-4 inhibitor TAK242. Our results suggest that Pg-LPS decreases the level of astrocytic p75NTR and then downregulates BDNF maturation, leading to depression-like behavior in mice. Our study provides the first evidence that Pg is a modifiable risk factor for depression and uncovers a novel therapeutic target for the treatment of depression.
许多横断面流行病学研究表明，牙周炎的发病率与抑郁症的发病率呈正相关。然而，它们的因果关系和潜在机制在很大程度上尚不清楚。牙龈卟啉单胞菌（Pg）是牙周炎的主要病原体。我们用每隔一天给雌性小鼠注射 Pg 来处理 4 周，发现 Pg 处理的小鼠表现出明显的抑郁样行为、海马体中活化星形胶质细胞数量增加以及成熟脑源性神经营养因子（BDNF）和星形胶质细胞 p75NTR 水平降低。BDNF 海马体注射和星形胶质细胞中 p75NTR 的过表达均可缓解 Pg 诱导的小鼠抑郁样行为。此外，Pg-脂多糖（LPS）产生了类似的表型，这些表型可被 TLR-4 抑制剂 TAK242 逆转。我们的研究结果表明，Pg-LPS 降低了星形胶质细胞 p75NTR 的水平，从而下调了 BDNF 的成熟，导致小鼠出现抑郁样行为。我们的研究首次提供了证据表明 Pg 是抑郁症的可改变风险因素，并揭示了治疗抑郁症的新的治疗靶点。
