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

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Τίτλος: Could the Urease of the Gut Bacterium Proteus mirabilis Play a Role in the Altered Gut–Brain Talk Associated with Parkinson's Disease?
Συγγραφείς: Grahl, Matheus V. C., Andrade, Brenda da Silva, Perin, Ana Paula A., Neves, Gilda A., Duarte, Laura de Souza, Uberti, Augusto Frantz, Hohl, Kelvin Siqueira, Follmer, Cristian, Carlini, Celia Regina
Πηγή: Microorganisms; Aug2023, Vol. 11 Issue 8, p2042, 29p
Θεματικοί όροι: Parkinson's disease, Proteus (Bacteria), Alpha-synuclein, Tyrosine hydroxylase, Membrane permeability (Biology), Urease
Περίληψη: 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 (PmUreβ) in the pathogenesis of PD was assessed. Purified proteins were given to mice intraperitoneally (20 μg/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-α and IL-1β were measured in Caco2 cells and cellular permeability was assayed in Hek 293. The proteins were incubated in vitro with α-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 α-synuclein and tyrosine hydroxylase decreased. PMU increased the pro-inflammatory cytokines and altered the cellular permeability in cultured cells. The urease, but not the PmUreβ, altered the morphology of α-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. [ABSTRACT FROM AUTHOR]
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Βάση Δεδομένων: Complementary Index
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  Data: Could the Urease of the Gut Bacterium Proteus mirabilis Play a Role in the Altered Gut–Brain Talk Associated with Parkinson's Disease?
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  Data: Microorganisms; Aug2023, Vol. 11 Issue 8, p2042, 29p
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  Data: <searchLink fieldCode="DE" term="%22Parkinson's+disease%22">Parkinson's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Proteus+%28Bacteria%29%22">Proteus (Bacteria)</searchLink><br /><searchLink fieldCode="DE" term="%22Alpha-synuclein%22">Alpha-synuclein</searchLink><br /><searchLink fieldCode="DE" term="%22Tyrosine+hydroxylase%22">Tyrosine hydroxylase</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+permeability+%28Biology%29%22">Membrane permeability (Biology)</searchLink><br /><searchLink fieldCode="DE" term="%22Urease%22">Urease</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: 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 (PmUreβ) in the pathogenesis of PD was assessed. Purified proteins were given to mice intraperitoneally (20 μg/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-α and IL-1β were measured in Caco2 cells and cellular permeability was assayed in Hek 293. The proteins were incubated in vitro with α-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 α-synuclein and tyrosine hydroxylase decreased. PMU increased the pro-inflammatory cytokines and altered the cellular permeability in cultured cells. The urease, but not the PmUreβ, altered the morphology of α-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. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Microorganisms is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/microorganisms11082042
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        Text: English
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              Text: Aug2023
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