"Brain training" improves cognitive performance and survival in a transgenic mouse model of Huntington's disease

Environmental enrichment (EE) has been shown to improve neurological function and cognitive performance in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We have shown recently that even when they are already living in an enriched environment, additional EE had beneficial effects in R6/2 mice. Here we examined the effects of three different enrichment paradigms on cognitive dysfunction in R6/2 mice in a longitudinal study. The EE consisted of either enforced physical exercise on the Rotarod (predominantly motor stimulation), training in a novel type of maze, the 'noughts and crosses' (OX) maze (mainly cognitive stimulation), or access to a playground, that gave the mice the opportunity for increased, self-motivated activity using running wheels and other toys in a social context (mixed EE). We designed the OX maze to test spatial memory in the R6/2 mouse while minimizing motor demands. Control mice remained in their home cages during the training period. Mice were given enrichment between 6 and 8 weeks of age, followed by cognitive (Lashley maze) and motor testing (Rotarod) between 8 and 10 weeks. Mice were then given a further period of enrichment between 10 and 12 weeks, and their behavior was re-tested between 12 and 14 weeks of age. We also collected body weights and age at death from all mice. The OX maze was as sensitive for detecting learning deficits in the R6/2 mice as other types of mazes (such as the Morris water maze). Interestingly, providing cognitive stimulation via training in the OX maze produced significant improvements in subsequent cognitive performance by male, but not female, R6/2 mice in the Lashley maze task. OX maze training also significantly improved loss of body weight and survival in male R6/2 mice. These effects became apparent after as little as 2 weeks of training in the OX maze. These data suggest that there is a cognitive reserve that may be exploited in neurodegenerative disease. While brain training was not beneficial for all mice, it produced no deleterious effects, and so warrants further study in rodent models of HD.