Motor, emotional and cognitive deficits in adult BACHD mice: A model for Huntington's disease

Abstract

RationaleHuntington's disease (HD) is characterized by progressive motor dysfunction, emotional disturbances and cognitive deficits. It is a genetic disease caused by an elongation of the polyglutamine repeats in the huntingtin gene. Whereas HD is a complex disorder, previous studies in mice models have largely been confined to assessing motor deficits. ObjectivesThe aim of the present studies is a comprehensive phenotypical assessment of not only motor and gait deficits, but also of emotional and cognitive deficits in adult BACHD mice. Material and methods46 male BACHD mice between 9 and 10 months of age were used. Wild type (+/+) and transgenic (+/T) mice were tested for motor deficits on a Rotarod and Catwalk system. Emotional deficits were assessed with the zero-maze and fear conditioning tests. Cognitive deficits in a strategy shifting task were evaluated in a cross-maze test. ResultsComparing +/T and +/+ mice, we replicated the motor deficits in the transgenic mice that were previously described in the Rotarod test. For the first time, motor coordination imbalances in +/T animals are described in the Catwalk gait analysis system. +/T mice showed more anxiety-like behavior in the zero-maze test and a higher freezing response in the fear conditioning test. Reversal and strategy shifting impairments were demonstrated in the cross-maze, indicative of a disturbed prefrontal–striatal pathway. ConclusionThe results suggest that BACHD mice represent an animal model with a high degree of face validity for HD and may be very useful for testing novel therapeutic strategies.