Abstract
Recently, studies on the relationship between gut dysbiosis and Parkinson’s disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.
Highlights
Parkinson’s disease (PD) is a progressive neurological disease, accompanied by motor symptoms, such as rigidity, bradykinesia, tremor, and postural abnormalities, due to degeneration of dopaminergic and γ-aminobutyric acid neurons in the basal ganglia, including substantia nigra (SN)[1,2,3]
In the case of PD, a recent evidence reported that short chain fatty acids produced by gut microbiota promote α-synuclein-mediated gliosis and PD motor symptoms[23]
We observed that gut microbiota dysbiosis had occurred regardless of toxin type in the colons of neurotoxin-induced PD mice
Summary
Parkinson’s disease (PD) is a progressive neurological disease, accompanied by motor symptoms, such as rigidity, bradykinesia, tremor, and postural abnormalities, due to degeneration of dopaminergic and γ-aminobutyric acid neurons in the basal ganglia, including substantia nigra (SN)[1,2,3]. Previous studies on pathological changes in the intestine of PD patients and PD animal models suggest the possibility that gut alteration is associated with PD pathogenesis Both accumulated α-synuclein and 3-nitrotyrosine, which induce apoptotic cell death in dopaminergic neurons[11], are increased significantly in colonic submucosal nerve fibers of early PD subjects versus healthy controls[12,13]. Levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were increased in colonic tissues from 6-hydroxydopamine (6-OHDA)-lesioned PD rats[20] Taken together, these previous studies suggest that intestinal pathological changes may influence the pathogenesis of PD. We examined how this bacterium injured dopaminergic neurons by assessing the changes of inflammatory factors and α-synuclein in the brain as well as in the colon
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