Presentation Type

Poster

Faculty Mentor’s Full Name

Sarah Certel

Faculty Mentor’s Department

Division of Biological Sciences

Abstract / Artist's Statement

Animals often behave in ways that align with the underlying social structure of their species. Existing lower in the social hierarchy can have negative consequences for health and well-being, including changes in appetite and depression-like symptoms (Becker et al., 2008). In Drosophila melanogaster, the male social hierarchy is determined by aggressive encounters in which one fly becomes a dominant winner and one becomes a submissive loser. Interestingly, flies that have previously lost a fight are more likely to lose the next one (Yurkovic et al., 2006). This adoption of a “loser” phenotype in turn affects other behaviors such as courtship and is associated with neuronal signaling changes in the brain (Kim et al., 2018). Due to the reported changes in appetite following stressful social interactions, the focus of our project is to determine how losing fights may lead to adverse changes in the gut. In recent years, a growing consensus of the importance of the gut-brain axis on influencing decision-making and behavior has emerged. In our system we can ask, how does gene expression and function of the gastrointestinal (GI) system change when a male loses consecutive fights? To investigate this question, we will induce the loser phenotype by fighting pairs of naive Drosophila males and then analyzing changes in feeding behavior, intestinal stem cell (ISC) composition, and gene expression within the gut. Marked males were subject to a fighting assay consisting of three 20-minute fights to produce losers. Feeding assays will be conducted to measure differences in food intake between losers and controls. Loser and control guts will be dissected within 20-24 hours post fighting assay. Immunohistochemistry experiments to identify stem cell proliferation changes will be performed as well as RNA-seq analysis, which provides a readout of gene expression changes by quantifying RNA transcripts. We hypothesize that the loser male will eat less due to a reduced appetite, and this will be reflected in a reduction of transcript levels in genes related to satiety signaling. We also predict that losing will alter the number of ISCs in the posterior midgut. A greater understanding of how social stress-induced pathological behavior changes manifest at the cellular level will help in identifying therapeutic targets capable of mitigating these behaviors.

References

Becker, C., Zeau, B., Rivat, C. et al. (2008). Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Mol. Psychiatry. 13, 1079–1092. doi: 10.1038/sj.mp.4002097

Kim, Y. K., Saver, M., Simon, J., Kent, C. F., Shao, L., Eddison, M., Agrawal, P., Texada, M., Truman, J. W., and Heberlein, U. (2018). Repetitive aggressive encounters generate a long- lasting internal state in Drosophila melanogaster males. Proc. Natl. Acad. Sci. U. S. A. 115(5), 1099–1104. doi: 10.1073/pnas.1716612115

Yurkovic, A., Wang, O., Basu, A. C., and Kravitz, E. A. (2006). Learning and memory associated with aggression in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 103, 17519–17524. doi: 10.1073/pnas.0608211103

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Life Sciences

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Apr 19th, 10:45 AM Apr 19th, 11:45 AM

Once a Loser, Always a Loser: Effects of Social Defeat in Fruit Flies

UC South Ballroom

Animals often behave in ways that align with the underlying social structure of their species. Existing lower in the social hierarchy can have negative consequences for health and well-being, including changes in appetite and depression-like symptoms (Becker et al., 2008). In Drosophila melanogaster, the male social hierarchy is determined by aggressive encounters in which one fly becomes a dominant winner and one becomes a submissive loser. Interestingly, flies that have previously lost a fight are more likely to lose the next one (Yurkovic et al., 2006). This adoption of a “loser” phenotype in turn affects other behaviors such as courtship and is associated with neuronal signaling changes in the brain (Kim et al., 2018). Due to the reported changes in appetite following stressful social interactions, the focus of our project is to determine how losing fights may lead to adverse changes in the gut. In recent years, a growing consensus of the importance of the gut-brain axis on influencing decision-making and behavior has emerged. In our system we can ask, how does gene expression and function of the gastrointestinal (GI) system change when a male loses consecutive fights? To investigate this question, we will induce the loser phenotype by fighting pairs of naive Drosophila males and then analyzing changes in feeding behavior, intestinal stem cell (ISC) composition, and gene expression within the gut. Marked males were subject to a fighting assay consisting of three 20-minute fights to produce losers. Feeding assays will be conducted to measure differences in food intake between losers and controls. Loser and control guts will be dissected within 20-24 hours post fighting assay. Immunohistochemistry experiments to identify stem cell proliferation changes will be performed as well as RNA-seq analysis, which provides a readout of gene expression changes by quantifying RNA transcripts. We hypothesize that the loser male will eat less due to a reduced appetite, and this will be reflected in a reduction of transcript levels in genes related to satiety signaling. We also predict that losing will alter the number of ISCs in the posterior midgut. A greater understanding of how social stress-induced pathological behavior changes manifest at the cellular level will help in identifying therapeutic targets capable of mitigating these behaviors.

References

Becker, C., Zeau, B., Rivat, C. et al. (2008). Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Mol. Psychiatry. 13, 1079–1092. doi: 10.1038/sj.mp.4002097

Kim, Y. K., Saver, M., Simon, J., Kent, C. F., Shao, L., Eddison, M., Agrawal, P., Texada, M., Truman, J. W., and Heberlein, U. (2018). Repetitive aggressive encounters generate a long- lasting internal state in Drosophila melanogaster males. Proc. Natl. Acad. Sci. U. S. A. 115(5), 1099–1104. doi: 10.1073/pnas.1716612115

Yurkovic, A., Wang, O., Basu, A. C., and Kravitz, E. A. (2006). Learning and memory associated with aggression in Drosophila melanogaster. Proc. Natl. Acad. Sci. U. S. A. 103, 17519–17524. doi: 10.1073/pnas.0608211103