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). In order to test whether pathogenic microorganisms present within the gut trigger PD-like pathology, we will transfer Corynebacteria amycolatum (identified through the work of the Partnering Project) to GF and SPF Thy1-SNCA mice and assay for inflammation, striatal dopamine loss, behavioral deficits, and dopamine cell loss. During the last research period, we obtained and bred Thy1-SNCA transgenic mice in both our traditional mouse colony and the gnotobiotic facility. We have successfully established stablemouse 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. 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. In the next cycle, we plan confirm colonization in both germ free and specific pathogen free colonies of mice and will examine their effect on neuroinflammation and behavioral deficits during an early time period of PD progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1124307
Entities
People
- David G. Standaert
Organizations
- University of Alabama