Could the Urease of the Gut Bacterium Proteus mirabilis Play a Role in the Altered Gut-Brain Talk Associated with Parkinson's Disease?

Intestinal dysbiosis seems to play a role in neurodegenerative pathologies. Parkinson's disease (PD) patients have an altered gut microbiota. Moreover, mice treated orally with the gut microbe Proteus mirabilis developed Parkinson's-like symptoms. Here, the possible involvement of P. mirabilis urease (PMU) and its B subunit (PmUre beta) in the pathogenesis of PD was assessed. Purified proteins were given to mice intraperitoneally (20 mu g/animal/day) for one week. Behavioral tests were conducted, and brain homogenates of the treated animals were subjected to immunoassays. After treatment with PMU, the levels of TNF-alpha and IL-1 beta were measured in Caco2 cells and cellular permeability was assayed in Hek 293. The proteins were incubated in vitro with alpha-synuclein and examined via transmission electron microscopy. Our results showed that PMU treatment induced depressive-like behavior in mice. No motor deficits were observed. The brain homogenates had an increased content of caspase-9, while the levels of alpha-synuclein and tyrosine hydroxylase decreased. PMU increased the pro-inflammatory cytokines and altered the cellular permeability in cultured cells. The urease, but not the PmUre beta, altered the morphology of alpha-synuclein aggregates in vitro, forming fragmented aggregates. We concluded that PMU promotes pro-inflammatory effects in cultured cells. In vivo, PMU induces neuroinflammation and a depressive-like phenotype compatible with the first stages of PD development.