Date of Award

5-7-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Dr. Kim Huhman

Second Advisor

Dr. Benoit Chassaing

Third Advisor

Dr. Anne Murphy

Fourth Advisor

Dr. Elliott Albers

Fifth Advisor

Dr. Geert de Vries

Abstract

Social stress exacerbates symptoms of mood and anxiety disorders in humans. Here, we tested the hypothesis that social stress increases anxiety- and depression-like responses via changes in gut microbiota and inflammation. We used a social defeat model in Syrian hamsters to determine whether exposure to social stress alters the gut microbial community. We then tested whether alterations in the gut microbial community impacts susceptibility to social stress, and, if so, whether it might do so via immunological pathways. In Aim 1, the gut microbial community of hamsters was assessed by 16S mRNA Illumina sequencing after one and repeated agonistic encounters. Both dominant and subordinate hamsters exhibited alterations in the gut microbial community and reductions in species richness following social stress. LEfSE analysis revealed that some microbial taxa correlated with achieving dominant or subordinate status in a future agonistic encounter. In Aim 2, hamsters were treated with either a probiotic for 2 weeks or an emulsifier for 12 weeks to test whether manipulating gut microbiota impacts behavioral susceptibility to social defeat. Probiotics are thought to promote a healthy microbial composition and emulsifiers have been shown to disrupt the gut microbial community. Probiotic treatment increased avoidance behavior and decreased social interaction following defeat. Probiotic treatment also altered the gut microbial community and serum cytokines following defeat. Emulsifier treatment had no effect on behavior. In Aim 3, neuroinflammation was assessed following social defeat. There was no increase in microglial activation in brain following defeat suggesting that exposure to mild social stress in hamsters does not induce robust neuroinflammation. As a positive control, we examined microglial activation following administration of lipopolysaccharide, a bacterial endotoxin, and were able to demonstrate a robust inflammatory response in hamster brain. Thus, the experiments in Aim 3 suggest that neuroinflammation is not necessary for behavioral responses to social stress in hamsters. Collectively, these data demonstrate that exposure to social stress can alter gut microbiota and that the microbiota can alter susceptibility to social stress. Future studies will be necessary to determine the mechanisms underlying this two-way relationship.

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