Behavioral Testing for Therapeutic Outcome Measurements in an Animal Model of Huntington's Disease

ABSTRACT

OBJECTIVE: To investigate which outcome measurements are useful for detecting functional changes after therapeutic approach to delayed motor impairment in an animal model of Huntington's disease (HD). METHOD: R6/2 transgenic mice received intraventricular injections of adenoviral BDNF/noggin (AdB/N), AdBDNF, AdNull (n=15 each) at 4 weeks of age. Untreated R6/2s and wild-type mice were also recruited as controls. Motor performance was measured using rotarod analysis and locomotor activity test at regular intervals until preterminal age of 13 weeks. RESULTS: On constant speed rotarod testing, AdB/N-treated R6/2s exhibited a delayed disease progression after post- operative 6 weeks. AdB/N also ameliorated general locomotor activity deficits. One min-rotarod analysis showed a delayed motor impairment in AdBDNF group at preterminal age compared with AdNull and untreated controls, which was not shown in 3 min and 5 min-rotarod. Accelerating rotarod paradigm was not superior to constant speed. Partial therapeutic effects on locomotor activities were detected in total 60 min-monitoring, but not in 30 min- or 10 min- monitoring. CONCLUSION: Appropriate behavioral testing and outcome measurements should be selected to detect the treatment effect to slow functional deterioration in HD.