Fig. 2. Metformin treatment ameliorates the neuropsychiatric and motor behavior phenotype in heterozygous zQ175 mice.

Different behavioral tests were analyzed in 3-month-old mice (pretreatment) and after 3 months of treatment (6-month-old; post treatment). a Huntington disease (HD) and control mice were subjected to the tail suspension test, and the immobility time was measured (see Materials and methods). HD mice showed a depressive state as early as 3 months of age, which was worse in 6-month-old animals. However, when the mice were treated with metformin, their depression-related behavior became similar to that in wild-type (WT) animals (p < 0.037). b HD and control animals were subjected to the beam balance test. The time to cross each beam was recorded. HD mice exhibited difficulties crossing beams of different widths compared to WT animals (30 mm: p < 0.001; 12 mm: p < 0.001; and 5 mm: p < 0.001). In contrast, HD mice treated with metformin showed a reduced latency to cross the beam in comparison to non-treated mice (p = 0.014), and the values were similar to those for WT controls in the case of the 5 mm width beam (p = 0.822). c Rotarod experiments were performed with HD and control mice as described in the Materials and methods. Three-month-old HD animals had similar motor coordination to WT mice, although this motor behavior worsened with age (p < 0.001). However, when HD animals were treated with metformin, they showed higher latency to fall (p < 0.001), and they maintained a similar motor behavior to WT mice (p = 0.795). Values are the mean, and bars indicate the confidence interval (95% CI)