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. 2021 Sep 6;12:5305. doi: 10.1038/s41467-021-25651-y

Fig. 2. CHIR99021 is protective in HD animal models.

Fig. 2

a Timeline of CHIR99021 treatment in R6/2 mice. CHIR99021 was intraperitoneally injected from 6 to 12 weeks old. b Survival of R6/2 mice from 6 to 12 weeks old was analyzed by the Log-rank (Mantel–Cox) test (two-tailed). c One hour of movement activity of R6/2 and WT littermates was determined by open-field activity chamber at 9 weeks old. Total traveled distance is shown. WT Veh n = 22, WT CHIR n = 15, R6/2 Veh n = 16, R6/2 CHIR n = 15 mice/group. d Hindlimb clasping activity was assessed using the tail suspension test once a week from 9 to 12 weeks old. n = 10–15 mice/group. e DARPP-32 immunodensity was examined in the dorsolateral striatum of mice. Scale bar = 100 µm. WT Veh n = 3, R6/2 Veh n = 3, R6/2 CHIR99021 n = 5 mice/group. f Brain sections were stained with anti-Htt antibodies (clone EM48), and mtHtt aggregate numbers were quantified. Scale bar = 50 μm. R6/2 Veh n = 3, R6/2 CHIR99021 n = 4 mice/group. g Timeline of CHIR99021 treatment in YAC128 mice. CHIR99021 was intraperitoneally injected from 9 to 12 months old. h Rotarod performance of mice was assessed at the indicated ages. WT Veh n = 10, WT CHIR n = 13, YAC128 Veh n = 15, YAC128 CHIR n = 15 mice/group. i DARPP-32 immunodensity in the striatum of 12-month-old YAC128 and WT mice. Left: representative image. Scale bar = 50 μm. Right: histogram of relative DARPP-32 immunodensity. n = 7 mice/group. j Quantification of mtHtt aggregates in YAC128 and WT mice. Left: representative images, scale bar = 50 μm. Right: quantification of mtHtt aggregates. n = 9 mice/group. All values are reported as mean ± SEM. Data are representative of at least three independent experiments. Data were compared using one-way ANOVA with Tukey’s post hoc test in c, e, h, i, and the unpaired Student’s t test (two-tailed) in d, f, j. Exact p values are shown in the figures.