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Related Experiment Video

Updated: May 27, 2025

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Chronic urinary tract infections cause persistent microglial changes in a humanized ɑ-synuclein mouse model.

Gabriela Mercado1,2, Ann-Céline Clabout3, Vanessa Howland1

  • 1Parkinson's Disease Center, Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA.

Journal of Parkinson'S Disease
|February 17, 2025
PubMed
Summary

Recurrent urinary tract infections (UTIs) trigger lasting neuroinflammation and motor deficits in a mouse model, suggesting a link to synucleinopathies like Parkinson's disease.

Keywords:
Parkinson's diseasemultiple system atrophyneuroinflammationsynucleinsynucleinopathiesurinary tract infections

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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Neurology

Background:

  • Urinary tract infections (UTIs) are increasingly linked to synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA).
  • UTIs occur more frequently in PD and MSA patients than the general population, preceding clinical diagnosis.
  • The mechanisms connecting UTIs to PD and MSA pathogenesis remain unclear.

Purpose of the Study:

  • To investigate the neuroinflammatory effects of recurrent UTIs on the brain.
  • To evaluate the impact of chronic UTIs on synucleinopathy development and progression.

Main Methods:

  • A humanized mouse model expressing alpha-synuclein was utilized.
  • Mice were subjected to repeated administration of uropathogenic *E. coli* to induce chronic UTIs.
  • Neuroinflammation and behavioral changes were assessed in response to chronic UTIs.

Main Results:

  • Recurrent UTIs induced persistent neuroinflammatory changes in key brain areas, including the dorsal vagal complex and cingulate cortex.
  • Mice exhibited behavioral motor deficits correlating with microglial activation in affected brain regions.
  • A chronic UTI phenotype with persistent bacteriuria was established in the mouse model.

Conclusions:

  • Recurrent UTIs can induce lasting neuroinflammation and motor alterations in the brain.
  • These findings highlight the potential role of UTIs in the progression of synucleinopathies and related neurological disorders.
  • Further research is warranted to explore the causal link between UTIs and neurodegenerative diseases.