RATIONALE: Huntington'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. OBJECTIVES: The 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 METHODS: 46 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. RESULTS: Comparing +/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. CONCLUSION: The 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.
RATIONALE: Huntington'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. OBJECTIVES: The 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 METHODS: 46 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. RESULTS: Comparing +/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. CONCLUSION: The 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.
Authors: Fuat Balci; Stephen Oakeshott; Jul Lea Shamy; Bassem F El-Khodor; Igor Filippov; Richard Mushlin; Russell Port; David Connor; Ahmad Paintdakhi; Liliana Menalled; Sylvie Ramboz; David Howland; Seung Kwak; Dani Brunner Journal: PLoS Curr Date: 2013-07-11
Authors: Ivan Rattray; Edward J Smith; William R Crum; Thomas A Walker; Richard Gale; Gillian P Bates; Michel Modo Journal: PLoS One Date: 2013-12-19 Impact factor: 3.240