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Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice

BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is...

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Autores principales: Feng, Yu-Kun, Wu, Qiong-Li, Peng, Yan-Wen, Liang, Feng-Yin, You, Hua-Jing, Feng, Yi-Wei, Li, Ge, Li, Xue-Jiao, Liu, Shu-Hua, Li, Yong-Chao, Zhang, Yu, Pei, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677837/
https://www.ncbi.nlm.nih.gov/pubmed/33213462
http://dx.doi.org/10.1186/s12974-020-02027-5
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author Feng, Yu-Kun
Wu, Qiong-Li
Peng, Yan-Wen
Liang, Feng-Yin
You, Hua-Jing
Feng, Yi-Wei
Li, Ge
Li, Xue-Jiao
Liu, Shu-Hua
Li, Yong-Chao
Zhang, Yu
Pei, Zhong
author_facet Feng, Yu-Kun
Wu, Qiong-Li
Peng, Yan-Wen
Liang, Feng-Yin
You, Hua-Jing
Feng, Yi-Wei
Li, Ge
Li, Xue-Jiao
Liu, Shu-Hua
Li, Yong-Chao
Zhang, Yu
Pei, Zhong
author_sort Feng, Yu-Kun
collection PubMed
description BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-02027-5.
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spelling pubmed-76778372020-11-20 Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice Feng, Yu-Kun Wu, Qiong-Li Peng, Yan-Wen Liang, Feng-Yin You, Hua-Jing Feng, Yi-Wei Li, Ge Li, Xue-Jiao Liu, Shu-Hua Li, Yong-Chao Zhang, Yu Pei, Zhong J Neuroinflammation Research BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-02027-5. BioMed Central 2020-11-19 /pmc/articles/PMC7677837/ /pubmed/33213462 http://dx.doi.org/10.1186/s12974-020-02027-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Feng, Yu-Kun
Wu, Qiong-Li
Peng, Yan-Wen
Liang, Feng-Yin
You, Hua-Jing
Feng, Yi-Wei
Li, Ge
Li, Xue-Jiao
Liu, Shu-Hua
Li, Yong-Chao
Zhang, Yu
Pei, Zhong
Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title_full Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title_fullStr Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title_full_unstemmed Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title_short Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
title_sort oral p. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in lrrk2 r1441g mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677837/
https://www.ncbi.nlm.nih.gov/pubmed/33213462
http://dx.doi.org/10.1186/s12974-020-02027-5
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