In BALB/c mice, H. hepaticus was linked to worse gut and brain pathology, disruption, inflammation, DNA damage, and beta-amyloid deposition.
Evidence
Preclinical infection study compared wild-type and CdtB-mutant H. hepaticus in BALB/c mice at 6 and 12 months using histology and molecular brain and gut assays.
Caveat
Because this is a mouse infection model with no bacterial DNA detected in brain, it cannot establish that the same CdtB-driven process causes human neurodegenerative disease.
Simplified
BACKGROUND: infection has been linked to neurodegenerative diseases, but the underlying molecular mechanism is still unclear. In this study, we established an animal model of neurodegeneration via infecting BALB/c mice with wild-type(WT) and -mutant (ΔCdtB) strains to investigate the influence of CdtB on the progression of cerebral injury. Helicobacter hepaticus H. hepaticus
METHODS: BALB/c mice were infected with either WT or ΔCdtB, and then were euthanized at 6- and 12- months post of infection (MPI). By means of histopathology and molecular biology techniques, we evaluated the colonization of, colonic and cerebral pathologies, extracellular fibrillary β-amyloid (Aβ) aggregates, antigen responses, (BBB) integrity, selected cytokines and proteins, as well as DNA damage. H. hepaticus
RESULTS: The findings proved thatsuccessfully colonized the intestines, whereas no bacterial DNA was observed in the brains of BALB/c mice. Nevertheless, CdtB antigen was identified in the brains of mice at sampling timepoint. During infection, CdtB exacerbated colonic and cerebral pathologies, compromised BBB integrity to amplify inflammatory responses in the brain, and modified the expression of critical neuronal proteins. Moreover, CdtB was found to induce DNA double-strand breaks (DSBs) and augment Aβ deposition in murine brains at 12 MPI. H. hepaticus
CONCLUSIONS: These data indicated thatinfection in BALB/c mice may serve as a novel model for studying neurodegenerative diseases. Furthermore,CdtB has the potential to exacerbate both neurodegenerative conditions and inflammatory responses. H. hepaticus H. hepaticus
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13099-025-00745-w.
