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 will create a germ-free (experimental) and specific pathogen free (control) preclinical mouse model in which alpha-synuclein is constitutively expressed under the Thy1 promotor (Thy1-SNCA). In order to test whether pathogenic microorganisms present within the gut trigger PD-like pathology, we will transfer corynebacterial to germ free and specific pathogen free Thy1-SNCA mice and assay for exacerbated inflammation, striatal dopamine loss, behavioral deficits, and dopamine cell loss. During this research period, we have obtained, bred, and transferred Thy1-SNCA transgenic mice in both our traditional mouse colony and the gnotobiotic facility. We have also confirmed alpha-synuclein expression via PCR and protein expression in the brain of Thy1-SNCA mice via western blot. In the next cycle, we plan to expand/breed both germ free and specific pathogen free colonies of mice, as well as confirm germ free and specific pathogen free status via sequencing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1092707
Entities
People
- David G. Standaert
Organizations
- University of Alabama at Birmingham