Background: Urinary tract infections (UTIs) have recently been linked to the onset of multiple synucleinopathies including Parkinson's disease (PD) and multiple system atrophy (MSA). UTIs are more common in people with PD or MSA, than in the general population and within these patient groups the incidence of UTIs is evenly distributed between men and women. UTIs are especially common during disease, but also in the years before clinical diagnosis.
Objective: The mechanisms by which UTIs may contribute to the development and progression of PD or MSA are not well understood. In this work, we evaluate the neuroinflammatory effects of recurrent UTIs on the brain.
Methods: In a humanized mouse model of ɑ-synuclein, we find that repeated administration of uropathogenic E. coli result in sustained UTIs, or a non-resolving chronic UTI phenotype with persistent bacteriuria. Using this model, we investigate the effects of repeated chronic UTIs on neuroinflammation and synucleinopathy in the brain.
Results: Recurrent UTIs lead to behavioral motor changes and are accompanied by persistent neuroinflammatory changes in multiple brain areas. Affected regions with microglial changes involve multiple lower brainstem areas responsible for sickness behavior, including the dorsal vagal complex, and the cingulate cortex.
Conclusions: These results suggests that recurrent UTIs can have lasting impact on the brain, and it warrants further investigation of the potential role of UTIs in the disease progression of synucleinopathies and related neurological disorders.
Keywords: Parkinson's disease; multiple system atrophy; neuroinflammation; synuclein; synucleinopathies; urinary tract infections.
This study explores how repeated urinary tract infections (UTIs) might influence the brain and contribute to the development of diseases like Parkinson's disease (PD) and multiple system atrophy (MSA). UTIs are common, especially in older adults and people with these neurodegenerative diseases, and they can worsen symptoms.A novel mouse model is established by repeatedly infecting mice with a type of bacteria known to cause UTIs in humans. We find that repeated infections lead to persistent UTIs and, more importantly, causes long-term inflammation in the brain. The areas of the brain affected by this inflammation are known to be involved in movement, pain regulation and sickness behavior.The findings suggest that chronic UTIs may not only be a symptom of PD and MSA but that they could also contribute to the progression of these diseases by causing ongoing brain inflammation. This inflammation might make the brain more vulnerable to further damage. Better understanding of these mechanisms could lead to new strategies for preventing or slowing the progression of these neurodegenerative diseases. The study highlights the need for more research to determine how managing UTIs could potentially protect the brain and improve outcomes for people at risk of or living with PD and MSA.