Research Symposium

BIO

I am a junior from Hollidaysburg, Pennsylvania, majoring in psychology and minoring in chemistry and biological sciences on the pre-medical track. My research interests lie in cellular neuroscience research and I plan to continue research in this area before starting medical school.

Chronic Semaglutide Treatment Reduces GLPIR-Mediated Activation of Hindbrain Neurons

Abstract

Glucagon-like peptide-1 (GLP1) is a hormone and neurotransmitter that acts on GLP1 receptors (GLP1R) in the body and brain to regulate glucose balance and food intake. Semaglutide (SEMA) and Exendin-4 are two GLP1R agonist drugs that act in the brain to reduce food intake. This project examines whether chronic SEMA treatment affects natural GLP1R protein in the brain, and whether it changes brain responses to acute delivery of Exendin-4. For this, 7 male rats received vehicle (VEH) injections and 8 received SEMA dose escalation (7-70 ug/kg BW) for 10 days followed by the maximum dose for 46 days. Four days after the final drug injection, rats were injected with Exendin-4 (10 ug/kg BW) 90 minutes before perfusion and brain harvest. Sections were processed for immunohistochemical localization of cFos (a marker of neural activation). Labeling was imaged on a Keyence microscope, then quantified using QuPath, with a focus on brain regions that contribute to appetite regulation and contain GLP1R. Data analysis revealed, chronic SEMA administration significantly reduces the ability of Ex4 to activate cFos in the AP (P = 0.01766), but does not significantly alter Fos within the NTS (p-value = 0.16708). Chronic SEMA appears to reduce GLPIR sensitivity within the AP. Results from this study suggest that chronic SEMA treatment alters brain responses to a different GLPIR agonist, Ex4. These results suggest that chronic SEMA may reduce GLP IR-mediated responses to natural, endogenously released GLP I in thousands of humans currently taking SEMA to treat diabetes and obesity.

Keywords: Chronic Semaglutide, GLP1, Area Postrema, NTS, cFos