Figure 4.

Study 2 behavior up to 30 weeks of age. (A) Experimental timeline for Study 2. Mice underwent a week-long baseline behavioral battery at 11 weeks old (B-D) prior to beginning twice weekly subcutaneous injections [0 or 5 mg/kg MnCl₂ • 4(H₂O)] at 12 weeks of age. The behavioral battery was repeated at 30 weeks of age (E-G), then half of the mice changed exposure groups at 31 weeks of age and behavioral battery was repeated at 50 weeks of age (see Fig. 5) prior to sacrifice and dissection (see Fig. 3.6) at 52 weeks of age. (B) Average latency to fall (3 trials per day; 300 s max per trial) from the rotarod across 3 days. Both genotypes displayed appropriate motor learning during the task, indicated by increased latency to fall on days 2 and 3 compared to day 1. YAC128 mice fall from the rod sooner than WT on all three days. Asterisks indicate a significant difference between genotypes on that day, and days that do not share a superscript letter are significantly different from each other within a genotype. (C) YAC128 mice spent less time in the open zone of the EZM compared to WT at 11 weeks of age, however this was driven by the 5 YAC128 mice that spent <100 s in the open zone and does not indicate anxiety-like behavior in either group. (D) YAC128 mice on average covered less distance than WT in 30 minutes of the open field, however the range of distance travelled is similar between genotypes. (E) Fold change in rotarod performance at baseline (11 weeks) to the 30-week assessment. Performance of each individual mouse at 30 weeks was divided by 11-week performance. On average there was a 25% decrease in performance for WT mice and 31% decrease for YAC128 mice. (F) There was no difference between genotypes or treatment groups for time spent in open zone of the EZM at 30 weeks. (G) Total distance travelled during 30 minutes in the open field. YAC128 mice travelled less than WT, but there was no effect of Mn after this length of exposure. For all, mean ± S.E.M. plotted unless otherwise noted. Asterisks * indicate genotype effect. * p <0.05, **, p<0.01, *** p<0.001, **** p<0.0001. n=26-29 per genotype-treatment group with approximately equal number of males and females.