Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes.
Brain Behav Immun
; 81: 523-534, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31299366
ABSTRACT
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 4â¯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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Bacteroidaceae
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Receptores de Fator de Crescimento Neural
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Porphyromonas gingivalis
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Fator Neurotrófico Derivado do Encéfalo
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Depressão
Tipo de estudo:
Observational_studies
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Prevalence_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Behav Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
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PSICOFISIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China