1. Effects of Gut Microbiota Alterations on Motor, Gastrointestinal, and Behavioral Phenotype in a Mouse Model of Parkinson's Disease.
- Author
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Radisavljevic N, Cirstea M, Bauer K, Lo C, Metcalfe-Roach A, Bozorgmehr T, Bar-Yoseph H, and Brett Finlay B
- Subjects
- Animals, Anti-Bacterial Agents, Disease Models, Animal, Mice, Mice, Transgenic, Phenotype, Gastrointestinal Diseases, Gastrointestinal Microbiome physiology, Parkinson Disease
- 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.
- Published
- 2022
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