Modeling gene-environment interactions in Parkinson's Disease: Helicobacter pylori infection of Pink1-/- mice induces CD8 T cell-dependent motor and cognitive dysfunction.
Kazanova, A.; Sung, J.; Oliveira, N. L.; Gavino, C.; Bessaiah, H.; Pei, J.; Burns, L.; Miller, W.; Brouillard-Galipeau, M.; Zhu, L.; Guerra, L. M.; Elemeery, M. N.; Recinto, S. J.; MacDonald, A.; Lanoix, J.; Thibault, P.; McBride, H. M.; Desjardins, M.; Stratton, J. A.; Labrecque, N.; Gruenheid, S.
Show abstract
Parkinsons disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of motor function. Diagnosis occurs late: after motor symptom development downstream of the irreparable loss of a large proportion of the dopaminergic neurons in the substantia nigra of the brain. Understanding PD pathophysiology in its pre-motor prodromal phase is needed for earlier diagnosis and intervention. Genetic risk factors, environmental triggers, and dysregulated immunity have all been implicated in PD development. Here, we demonstrate in a mouse model deficient in the PD-associated gene Pink, that infection with the human PD-associated gastric bacterium Helicobacter pylori leads to development of motor and cognitive signs resembling prodromal features of PD. This was also associated with proliferation and activation of primary mitochondria-reactive CD8 T cells and infiltration of CD8 T cells into the brain. Development of the motor and cognitive phenotypes in the infected Pink1-/- mice was abrogated when CD8 T cells were depleted prior to infection. We anticipate that this new model, which integrates genetic PD susceptibility, a PD-relevant environmental trigger, and specific immune changes that are required for symptom development, will be a valuable tool for increasing our understanding of this complex disease.
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