Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes

作者：Yixi Wang, Xiaoning Kang, Yang Cao, De‐Xiu Zheng, Yeming Lu, Chunfeng Pang, Zhi Wang, Bin Cheng, Yun Peng · 发表于：Brain Behavior and Immunity · 年份：2019 · DOI：10.1016/j.bbi.2019.07.012 · 被引用次数：43 · 研究领域：Nerve injury and regeneration、Stress Responses and Cortisol、Tryptophan and brain disorders

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.