Objective: While multiple animal models of Parkinson’s disease (PD) have been developed with varying applicability to different aspects of the disorder, no single model effectively mirrors all features of this complex disease. We aimed to provide further characterization of an existing transgenic mouse model of PD that displays motor symptoms and gastrointestinal (GI) involvement, by examining behavioral symptoms as well as gut microbiota composition over multiple timepoints.

Background: PD in humans is a multifaceted disorder consisting of GI dysfunction, gut microbiota alterations, and mood disorder comorbidities such as depression and anxiety, in addition to the classic motor symptoms. This complex disease is influenced by both genetic and environmental factors, and the variety of non-motor symptoms can greatly impact the quality of life of patients.

Method: A previously described transgenic mouse model of PD, dbl-PAC-Tg(SNCA^A53T)^+/+;Snca^-/-[1], was characterized in terms of motor and GI deficits, fecal microbiota composition, and behavioral alterations in comparison to a wild-type (WT) mixed strain with a similar genetic background. Furthermore, various timepoints were analyzed to better elucidate onset time and temporal trends in disease symptoms in this model.

Results: We found that transgenic mice displayed motor deficits in the rotarod, pole descent, and hindlimb clasping tests starting at 6 weeks of age and that these motor features were relatively stable up to 22 weeks of age. Transgenic mice also had increased transit time and reduced fecal water content indicating GI dysfunction. Behavioral alterations included increased exploratory behavior, and increased depression-like and apathy-like symptoms; this is the first report of behavioral alterations in this model. 16S microbiota sequencing of fecal samples revealed significant differences in microbiota composition, including a lower abundance of Prevotella in transgenic mice compared to WT controls.

Conclusion: Overall, this mouse model recapitulates multiple aspects of PD in humans, and is an especially useful tool for studying non-motor gastrointestinal and mood-related symptoms, making it an attractive choice for studying the gut-microbiota-brain axis in PD.

References: 1. Kuo et al. (2010) Human Molecular Genetics, 19(9). PMID 20106867.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/temporal-characterization-of-motor-gastrointestinal-and-behavioral-symptoms-in-a-snca-a53t-transgenic-mouse-model-of-parkinsons-disease/