Genetically Dissecting Neural Circuits Underlying Anorexia Nervosa
Abstract
Abnormal eating habits that drive excessive food seeking, or avoidance, can manifest as health-threatening and socially impactful eating disorders. Anorexia nervosa (AN) represents one of the most debilitating eating disorders with no effective cure and exhibits an array of core symptoms that include voluntary restrictive feeding, hyperactivity, and anxiety. In addition, AN frequently results from traumatic triggers and exhibits special penetrance in young females coinciding with estrogen surges, which is tightly associated with military personnel and their families. To date, the mechanistic understanding of AN has been greatly hindered by the lack of an effective animal model that faithfully recapitulates core symptoms in AN patients. Using a novel approach of chronic neuron activation, we have found that chronic activation of a group of hypothalamic neurons leads to core symptoms of AN, including voluntary restrictive feeding, anxiety, and frequent escape/jumping behaviors. Using multifaceted genetic, imaging, metabolic, and behavioral experimentation, we propose studies that will establish an effective model for AN research, and use this model toward better understanding AN. Such a model promises to help elucidate the critical, and yet unknown, circuit mechanisms by which hypothalamic neurons impact eating and associated emotional states and to identify pathophysiology responsible for AN development. Importantly, the proposed research will help reveal previously unidentified neural basis for the selective AN penetrance observed in young females and how AN is initiated by certain environmental triggers. Our results will also reveal key circuit bases for feeding abnormalities associated with AN, which often occurs in Service Members and Veterans, especially in young women encountering traumatic situations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310155
Entities
People
- Benjamin R Arenkiel
Organizations
- Baylor College of Medicine
- United States Army