Keywords

Huntington disease, reactive aggression, transgenic mouse model, Hu97/18 mice, amygdala; excitotoxic lesions.

Abstract

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a trinucleotide CAG expansion in the huntingtin gene (HTT). HD is characterized by motor, cognitive, and psychiatric symptoms that significantly impact patient and caregiver quality of life. Psychiatric symptoms, including depression, anxiety, and irritability, are common manifestations of HD and can emerge years before the onset is clinically diagnosed. Aggression is a common and challenging psychiatric symptom in HD, often misunderstood and associated with caregiver stress, early institutionalization, and reduced quality of life. Despite its clinical impact, aggression in HD lacks effective, targeted treatment options. Similar to HD patients, the Hu97/18 HD mouse model exhibits heightened aggression in response to non-threatening stimuli, suggesting this model can be used to investigate the neurological basis of HD-associated aggression, which could support development of targeted treatments that would improve quality of life for HD patients and caregivers. The amygdala mediates threat assessment and emotional responses such as fear and anger, making amygdala dysfunction a potential contributor to reactive aggression. To investigate the role of the amygdala in HD-associated aggression, we created bilateral excitotoxic lesions of the central amygdala of Hu97/18 mice. Compared to a sham control group, post-lesion, Hu97/18 mice continued to display reactive aggression, suggesting that the amygdala may not mediate HD-associated aggression. However, this cannot be concluded until lesions are validated, which is the goal of this study. To confirm lesion placement and assess size and severity, perfused brains were cryosectioned through the amygdala. Anatomical landmarks visible across serial sections were established to identify the span of the amygdala for collection. Two staining methods, cresyl violet (CV), which stains Nissl bodies, and Fluoro-Jade C (FJC), which stains dead or dying neurons were piloted. FJC was chosen because it allowed clearer visualization of the lesion. Lesion size did not differ between genotypes, but lesion severity was greater in Hu97/18 mice, suggesting increased susceptibility to excitotoxic damage. Neither lesion size nor severity were significantly associated with aggressive behavior in Hu97/18 mice, suggesting the amygdala is not the primary driver of HD-associated aggression, directing future research toward other relevant brain regions.

Thesis Completion Year

2026

Thesis Completion Semester

Summer

Thesis Chair

Southwell, Amber

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Neuroscience

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

Download

Share

COinS
 

Accessibility Statement

This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.