The effects of chronic simvastatin treatment on the expression of behavioral symptoms in a transgenic mouse model of Huntington’s disease

• Main Author: Whitmarsh, Ashley
• Format: Others
• Published: ScholarWorks@UNO 2013
• Subjects: Huntington's disease; Rhes; statin; mevalonate; Huntingtin protein; rotarod; Behavioral Neurobiology; Biochemistry; Biological Psychology
• Online Access: http://scholarworks.uno.edu/td/1773; http://scholarworks.uno.edu/cgi/viewcontent.cgi?article=2815&context=td

Huntington’s disease (HD) is a heritable, neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. An unstable CAG expansion within the gene normally encoding for the Huntingtin protein is responsible. The expanded mutant form of Huntingtin and the putative protein co-factor Rhes interact and cause cell death within the striatum. We hypothesized chronic treatment with simvastatin, a cholesterol lowering drug, would disrupt the biosynthetical pathway which gives both Rhes and its target cells binding sites and render Rhes inactive. Healthy and HD mice were treated with simvastatin or a vehicle. Animals’ motor behavior was assessed with three separate tests over the first four months of life. No significant differences were found between the HD groups; however, the HD treated animals’ performance on the rotarod test, at month 4, was intermediate between healthy mice and HD vehicle treated mice. The results hint at simvastatin’s therapeutic potential, but are interpreted cautiously.