Figure 1

Treatment with NAC delays the onset and progression of motor deficits in HD mice and has antidepressant-like effects in both HD and WT mice. (a) Analysis of the clasping phenotype showed a significant age × treatment × genotype interaction. Post hoc analyses revealed that NAC significantly delayed the onset of the clasping phenotype in HD mice, with saline-HD mice showing clasping behavior from 10 weeks onward, while NAC-HD mice did not show clasping behavior until 14 weeks. NAC-treated HD mice also showed significantly lower levels of clasping behavior relative to saline-treated HD mice from 11 weeks onward. (b) A significant age × treatment interaction was found in Rotarod. Post hoc analyses revealed that the treatment effect began at 12 weeks of age, with NAC-HD mice performing better than saline-HD mice from 11 weeks of age. There was also a significant age × genotype interaction, with post hoc analyses revealing that genotype deficits were present from 8 weeks of age, progressively worsening over the lifespan of the mice. (c) Representation of the different phases of stride that can be measured using the Digigait, including total stride, stance, swing, brake and propel duration. (d) A significant treatment × genotype interaction was found in the propel/brake ratio. Post hoc tests show that saline-HD mice have a higher ratio than both NAC-HD and saline-WT mice. (e) A significant treatment effect was seen in the time spent immobile during the FST, with NAC-treated mice spending less time immobile than saline-treated mice. Error bars represent mean±s.e.m.; n=10–14; treatment effects: *P<0.05, **P<0.01, ***P<0.001. FST, forced swim test; HD, Huntington’s disease; NAC, N-acetylcysteine; WT, wild type.