Journal Article

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

Peng, Yan-Wen, Li, Ge, Pei, Zhong, Feng, Yi-Wei, Zhang, Yu, Li, Yong-Chao, Feng, Yu-Kun, Wu, Qiong-Li, You, Hua-Jing, Li, Xue-Jiao, Liu, Shu-Hua, Liang, Feng-Yin

2020

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antibodies / Biomedical and Life Sciences / Biomedicine / Cellulose / Chronic periodontitis / Colon / Degeneration / Disease / Dopamine receptors / Dopaminergic neurons / Dysbacteriosis / Fluorides / Gene expression / Gum disease / Health aspects / IL-17A / IL-1β / Immune response / Immunology / Inflammatory diseases / Interleukin 17 / Intestinal microflora / Laboratory animals / Leucine / Leukocytes (mononuclear) / Lipopolysaccharides / LRRK2 protein / Manufacturers / Microbiota / Microbiota (Symbiotic organisms) / Microglia / Movement disorders / Nervous system / Neurobiology / Neurodegeneration / Neurodegenerative diseases / Neurology / Neurosciences / Oral administration / Parkinson's disease / Pathogenesis / Pathogens / Periodontal disease / Periodontitis / Permeability / Polymerase chain reaction / Proteins / R1441G LRRK2 / Risk factors / Software / Substantia nigra / Synuclein / Tumor necrosis factor-α / Zonula occludens-1 protein