Affiliations: [a] Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
| [b] Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
| [c] Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
Correspondence:
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Correspondence to: Dr. B. Brett Finlay, PhD, Michael Smith Laboratories, University of British Columbia, 2185 E Mall, Vancouver, BC, V6T 1Z4, Canada. Tel.: +1 604 822 2493; E-mail: [email protected].
Abstract: Background:Parkinson’s disease (PD) is a multi-system disorder consisting of not only classic motor symptoms but also a variety of non-motor symptoms including gastrointestinal (GI) dysfunction and mood disorders. The gut microbiota has been suggested to play a role in modulating PD motor and non-motor features, although the causality and mechanisms behind these proposed interactions remains largely understudied. Objective:In this study, we aimed to provide in-depth characterization of an established mouse model of PD (transgenic (TG) SNCA A53T) and experimentally address how changes to the gut microbiota impact the PD-like phenotype. Methods:We profiled the PD-like phenotype of transgenic mice through a panel of motor, GI, and behavioral tests. We then investigated how antibiotic treatment or gut microbial community transfer (via cohousing with wild-type mice) impacted the PD-like phenotype. Results:We found that this mouse model demonstrated early (6 weeks of age) motor symptoms when compared to a wild-type control mouse strain. Transgenic mice also exhibited early GI dysfunction, as well as behavioral alterations, including reduced anxiety-like behavior, and increased depression-like and apathy-like behavior. Compared to wild-type mice, the transgenic fecal microbiota was less diverse and compositionally distinct. Interestingly, drastic alterations to the gut microbiota, through antibiotic treatment or cohousing with wild-type mice, had a minimal effect on the motor, GI, and behavioral phenotype of transgenic mice. Conclusion:We concluded that this mouse model effectively recapitulates motor and non-motor features of PD; however, the gut microbiota appears to exhibit a minor impact on the pathophysiology of this PD model.
Keywords: Parkinson’s disease, genetic models, gut microbiota, microbiota-gut-brain axis
