Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Differential striatal gene expression profiles underlying the propensity for depression-like behaviour in a mouse model of vertical sleeve gastrectomy (#180)

Renee A Papaluca 1 2 , Eva Guerrero Hreins 1 2 , Aneta Stefanidis 3 , Claire Foldi 3 , Brian Oldfield 3 , Priya Sumithran 4 , Robyn M Brown 1
  1. School of Biomedical Sciences, Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, VIC, Australia
  2. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia
  3. Department of Physiology, Monash University , Melbourne
  4. Department of Surgery, School of Translational Medicine, Monash University, Melbourne

Introduction: Bariatric surgery is currently the most effective long-term treatment for obesity, resulting in reduced appetite and improved glycaemic control. These benefits are due to profound changes to the gut-brain axis. Despite these benefits, a small patient subset exhibits higher rates of adverse mental health outcomes post-surgery, such as depression and anxiety. Although emerging longitudinal studies explore this association, there is a paucity of research exploring how gut-brain axis alterations could mechanistically contribute to these adverse mental health outcomes post-surgery. Therefore, the aim of this study was to investigate individual differences in the effect of bariatric surgery on depressive-like and anxiety-like behaviour in a mouse model of vertical sleeve gastrectomy (VSG).

Materials and Methods: Male and female C57BL/6 (n=57) mice were fed a high-fat, high-sugar diet (45%kcal fat; 11 weeks) before undergoing VSG or sham surgery. Before and after surgery, mice were tested for depression-like and anxiety-like behaviour. RNA was extracted from tissue punches of the dorsal striatum, a brain region associated with depression, and subjected to next-generation bulk RNA-sequencing. Analysis of this data is currently ongoing.

Results: Compared to sham surgery mice, VSG resulted in significant and sustained weight loss, accompanied by reduced food intake. VSG mice also showed a trend for higher immobility times in the forced swim test and decreased preference for sucrose solution, suggestive of depressive-like behaviour. Results from analysis of RNA-sequencing of the dorsal striatum are pending

Conclusion: Outcomes from this study will provide valuable insight into the neurobiological underpinnings of adverse mental health outcomes following bariatric surgery.