Huntington Disease (HD) is a fatal neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although HD onset is determined by motor symptoms, psychiatric symptoms, like depression and aggression, can develop earlier, have a larger impact on quality of life, and are understudied due to stigma. Our lab has observed hyper aggression in our humanized HD mouse model (Hu97/18) compared to our knock-in HD mouse model (Q175FDN). We characterized these differences and found that the Hu97/18 mice overreact in neutral situations, behaving as if they are in threatening situations. We are now using this novel model of HD-related aggression to study its neurological basis. Increased reactive aggression has been linked to stress levels and the prefrontal cortex (PFC) due to its role in emotional regulation. This study seeks to determine if HD-related aggression is associated with increased stress levels and changes in the PFC. Our cortisol study shows that the Hu97/18 mice display significantly higher cortisol levels than baseline, suggesting a link between systemic stress and heightened aggression. Additionally, quantified PFC volumes show a moderate relationship between PFC volume and aggression in wild-type (WT) mice that is lost in the Hu97/18 mice. This data will help elucidate factors that modulate aggression in HD and may identify therapies with high potential to alleviate this devastating symptom in patients.
Southwell, Amber L.
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Vyas, Kadambari, "The Role of the Prefrontal Cortex and Stress in Huntington Disease-Mediated Aggression" (2022). Honors Undergraduate Theses. 1218.