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

A growing body of research suggests a link between immune system activation and the development of Parkinson’s disease (PD). Previous work showed that repeated gastrointestinal infection with Citrobacter rodentium can induce PD-like motor dysfunction in Pink1 knockout (KO) mice, along with immune cell infiltration into the brain. To better understand mechanisms underlying immune-mediated brain attack in this model, we tested whether mild infections are sufficient to increase blood-brain barrier (BBB) permeability and trigger brain inflammation. We show increased BBB permeability in both WT and KO mice, persistent microglial activation, increase levels of inflammatory cytokines and neutrophils infiltration in the brain. These findings support the hypothesis that even mild gastrointestinal infections can increase BBB permeability, disrupt brain homeostasis, and promote chronic neuroinflammation in genetically susceptible individuals contributing to subsequent induction of PD pathology with aging.