Could the Urease of the Gut Bacterium Proteus mirabilis Play a Role in the Altered Gut-Brain Talk Associated with...

Area of Science:

• Neuroscience
• Microbiology
• Immunology

Background:

• Intestinal dysbiosis is linked to neurodegenerative diseases like Parkinson's disease (PD).
• The gut microbe *Proteus mirabilis* has been associated with PD-like symptoms in mice.
• The role of specific bacterial components, such as *P. mirabilis* urease (PMU), in PD pathogenesis requires investigation.

Purpose of the Study:

• To investigate the involvement of *P. mirabilis* urease (PMU) and its B subunit (PmUreβ) in Parkinson's disease pathogenesis.
• To assess the effects of PMU on neuroinflammation, behavior, and alpha-synuclein aggregation.

Main Methods:

• Mice were treated intraperitoneally with purified PMU or PmUreβ.
• Behavioral tests were performed, and brain homogenates were analyzed for inflammatory markers, caspase-9, alpha-synuclein, and tyrosine hydroxylase.
• Cultured cells (Caco2 and Hek 293) were treated with PMU to measure cytokine levels and cellular permeability.
• In vitro experiments examined the interaction of PMU and PmUreβ with alpha-synuclein using transmission electron microscopy.

Main Results:

• PMU treatment induced depressive-like behavior in mice, without motor deficits.
• Increased caspase-9 and decreased alpha-synuclein and tyrosine hydroxylase levels were observed in the brains of PMU-treated mice.
• PMU elevated pro-inflammatory cytokines (TNF-α, IL-1β) and altered cellular permeability in cultured cells.
• PMU, but not PmUreβ, modified alpha-synuclein aggregate morphology in vitro, forming fragmented aggregates.

Conclusions:

• PMU promotes pro-inflammatory effects in vitro and induces neuroinflammation and a depressive-like phenotype in vivo.
• These findings suggest PMU may play a role in the early stages of Parkinson's disease development.
• The study highlights the potential contribution of gut microbial components to neurodegenerative processes.