Interactions of Gut Microbiome, Genetic Susceptibility, and Environmental Factors in Parkinson's Disease
Abstract
Genetic and environmental factors explain a fraction of Parkinson disease risk, prompting the question if microorganisms in the gut may be the trigger. The main goal of this proposal is to validate and investigate the mechanisms of interaction in a preclinical mouse model of PD. To do this, we have created a germ-free (GF) and specific pathogen free (SPF) pre-clinical mouse model in which alpha-synuclein is constitutively expressed under the Thy1 promotor (Thy1-SNCA). We have successfully established stable mouse colonies in both settings and both confirmed the transgene established alpha-synuclein expression via PCR and protein expression in the brain of Thy1-SNCA mice via western blot. In order to test whether pathogenic microorganisms present within the gut trigger PD-like pathology, we have transferred Corynebacteria amycolatum (identified through the work of the Partnering Project) to GF and SPF Thy1-SNCA mice. We have established cultured conditions for C. amycolatum, a PCR method to detect it, and performed initial transfers to both germ free and specific pathogen free mice. We have shown that in GF mice, this produces stable colonization. In the SPF mice, however, Corynebacteria amycolatum colonization does not occur. During the last research period, we have bred a colony of GF Thy1-SNCA transgenic mice sufficient to test the study outcomes. In the next cycle, we will complete the transfer of Corynebacteria amycolatum to these mice and assess and analyze the study outcomes in GF mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1156110
Entities
People
- Ashley Harms
- David G. Standaert
Organizations
- University of Alabama at Birmingham