Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Nancy M. Bonini

Abstract

Current studies suggest a relationship between microbes in the gut and the brain, including an impact on brain disease development, severity, and progression. However, exploring this relationship is hindered by the intricacies of mammalian models. Drosophila has the potential to be an excellent model organism for studies of the gut-brain axis due to the relative simplicity of its microbiome, similarity to mammals, and efficient methods to rear germ-free flies. To take advantage of this potential, I examined the gut-brain axis in Drosophila models of autosomal recessive parkinsonism and observed a five-fold increase in the gut microbial load of aged parkin animals. The microbial load of pink1 animals was unchanged, suggesting a Pink1-independent role for parkin in maintaining microbial load numbers within normal range. Conditional RNAi showed that parkin is required in gut enterocytes and not in neurons or muscle to maintain microbial load homeostasis. Germ-free parkin flies exhibited improved resistance to paraquat, suggesting an impact of the gut microbiome on toxin sensitivity in parkin flies. Sequencing of 16S rDNA revealed microbial species with altered relative abundance in parkin null flies compared to controls. These data reveal a role for parkin activity in maintaining microbial composition and abundance in the gut, suggesting a relationship between parkin function and the gut microbiome, and deepening our understanding of parkin and its mutant effects.

Embargoed

Available to all on Monday, January 18, 2021

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