Investigating Aggression in Huntington Disease

Huntington Disease (HD) is a neurodegenerative disorder that is caused by a CAG trinucleotide repeat expansion in the huntingtin gene. The onset of the disease is defined by the presence of motor deficits, such as chorea. However, cognitive and psychiatric symptoms often develop before motor onset and typically have a larger impact on patient quality of life. Psychiatric symptoms include depression, anxiety, and OCD, but also aggression and irritability, which have been comparatively understudied due to stigma. Currently, treatments to modify these behaviors in premanifest HD patients are not consistently effective and often have side effects, creating a need for research into these psychiatric disturbances. Our lab has observed increased-aggression in our humanized HD mouse model (Hu97/18) during routine handling that is not present in our knock-in HD mouse model (Q175FDN). In this study, we seek to quantify the aggressive behavior exhibited by these two mouse models and determine the neurological basis for these observed behavioral differences. From this analysis, we seek to identify potential therapeutic targets for modulating aggressive behavior in mice, which could lead to the development of therapies that reduce the aggressive behavioral symptoms experienced by HD patients