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

Wang, Yixi; Kang, Xiaoning; Cao, Yang; Zheng, De-Xiu; Lu, Yeming; Pang, Chunfeng; Wang, Zhi; Cheng, Bin; Peng, Yun

doi:10.1016/j.bbi.2019.07.012

Cited by 22 publications

(21 citation statements)

References 40 publications

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“…The proposed underlying mechanism was that P. gingivalis induced astrocyte activation and downregulated neurotrophic factor receptor p75 expression in a TLR4-dependent fashion, ultimately inhibiting the maturation of the brain derived of neurotrophic factor. This study has provided the first experimental evidence that P. gingivalis could be a risk factor for depression [ 106 ]. More studies are needed.…”

Section: Neurologymentioning

confidence: 99%

Porphyromonas gingivalis and Its Systemic Impact: Current Status

et al. 2020

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The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of Porphyromonas gingivalis in atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about Porphyromonas gingivalis and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which Porphyromonas gingivalis is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that Porphyromonas gingivalis should be regarded as a modifiable factor for several diseases.

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Section: Neurologymentioning

confidence: 99%

Porphyromonas gingivalis and Its Systemic Impact: Current Status

et al. 2020

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“…It is abundantly expressed during the early developmental stages of nerve cells, and induces cell proliferation, migration, differentiation, survival, apoptosis, synapse establishment, and nerve formation, and exerts multiple biological effects through different signal transduction pathways. A previous study showed that p75NTR might mitigate depression and prompt BDNF maturation [ 38 ], which may be counterproductive for PSD. Therefore, JNK and p75NTR are promising candidates as new therapeutic targets for PSD.…”

Section: Discussionmentioning

confidence: 99%

proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

et al. 2021

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Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.

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“…Indeed, neuroinflammation sustained by the chronic inflammation associated with periodontitis, increased systemic lipopolysaccharide and bacterial translocation from periodontal sites through a more permeable blood-brain barrier has been investigated [50,51]. The development of depression-like behavior with brain modifications was observed in mice with experimental periodontitis induced by oral gavage of Porphyromonas gingivalis, such as an increased number of activated astrocytes and decreased levels of mature brainderived neurotrophic factor and astrocytic p75NTR in the hippocampus [52]. Nevertheless, during periodontitis, cytokines, such as Il-1β, IL-6 and TNF-α, are secreted in response to bacterial insult and could sustain the neuroinflammation process after passage through the blood-brain barrier [34,50].…”

Section: Discussionmentioning

confidence: 99%

Influence of Depression and Anxiety on Non-Surgical Periodontal Treatment Outcomes: A 6-Month Prospective Study

Petit

Anadon-Rosinach

Tuzin

et al. 2021

IJERPH

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Periodontal treatment could be worsened by risk factors. Depression and anxiety have been suggested as potentially influencing periodontal treatment outcomes. The aim of this study was to determine their association with non-surgical periodontal treatment outcomes in patients with generalized severe periodontitis (stage III/IV generalized periodontitis) at 6 months. A total of 68 patients diagnosed with generalized severe periodontitis were treated with scaling and root planing (SRP) and were followed at 3 and 6 months. The data of the 54 patients that followed the entire protocol were considered for analysis. Depression and anxiety levels were determined at baseline by the Beck Depression Inventory (BDI) and State-Trait Inventory (STAI) questionnaires. The association between psychological scores and periodontal parameters was evaluated by multivariate analysis. At 3 and 6 months, SRP induced an improvement for all periodontal parameters (plaque index (PI), bleeding on probing (BOP), periodontal probing depth (PPD) and clinical attachment loss (CAL)). BDI and STAI scores were associated with the evolution of PI, BOP, mean PPD and number of sites with PPD > 3 mm and with CAL > 3 mm. Depression and anxiety should be considered as risk factors for SRP and the identification of at-risk patients should be performed using well-established tools.

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

Cited by 22 publications

References 40 publications

Porphyromonas gingivalis and Its Systemic Impact: Current Status

Porphyromonas gingivalis and Its Systemic Impact: Current Status

proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

Influence of Depression and Anxiety on Non-Surgical Periodontal Treatment Outcomes: A 6-Month Prospective Study

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