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

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.