A single Citrobacter rodentium infection in Pink1 knockout and wild type mice leads to regional blood-brain-barrier perturbation and glial activation without dopamine neuron axon terminal loss

This was not accompanied by any change in global expression of tight-junction proteins or in markers of the integrity of the dopamine (DA) system in the striatum at both time points. However, chronic microglial activation was detected at day 26 post infection, accompanied by an elevation of the inflammatory mediators eotaxin, IFNγ, CXCL9, IL-17 and MIP-2 in the striatum. Neutrophil infiltration in the brains of infected mice was also noted at day 26 post infection, as revealed by immune cell profiling by flow cytometry.

Our results support the hypothesis that even after mild gastro-intestinal infection, increased BBB permeability could contribute to perturbations of brain homeostasis including increased microglial activation and the establishment of a chronic state of brain inflammation. Such perturbations could potentially act as a first hit for subsequent induction of PD pathology in the context of genetic vulnerability.