Valeria Elena Derwartanian
Research Mentor: Martin Myers Jr
Mentor Department: Not Available, Medicine
Author(s): Not Available
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 33
Abstract
Growth Differentiation Factor 15 (GDF15) is a stress-induced cytokine that promotes anorexia, weight loss, and other sickness responses in many disease states, including cancer cachexia, and has also emerged as a potential therapeutic target for obesity. These effects are mediated by its receptor, GFRAL, which is expressed exclusively in the area postrema (AP) and nucleus of the solitary tract (NTS). Although Gfral neuron activation is known to suppress feeding and promote aversive responses, the regulation of the distinct Gfral AP and Gfral NTS neuronal populations remains poorly understood. This project aims to define the physiological and pathological regulators of Gfral AP and Gfral NTS neurons. We hypothesized that these neurons are preferentially activated by pathologic, rather than nutrient/ingestion-related, stimuli and that each population receives distinct presynaptic inputs reflecting specialized roles in sickness responses. To test this, we assessed FOS induction in Gfral AP and Gfral NTS neurons following ingestion-related versus pathologic stimuli. In the future, we will use Cre-dependent retrograde viral tracing in a Gfral-Cre rat model to identify and compare their upstream inputs. By defining how Gfral neurons are regulated, these studies will provide a critical foundation for understanding how this system can be modulated in both cachexia and obesity and will inform future strategies aimed at either inhibiting Gfral neurons to prevent cachexia or activating them to promote weight loss.
