FIG 9.

Survival, nesting scores, and scrapie severity scores of mice infected with scrapie strain RML and either treated with PLX5622 beginning at 80 dpi or left untreated. Mice were infected with scrapie strain RML and fed control chow (untreated, filled circles) or switched to chow supplemented with PLX5622 (open circles) after 80 dpi. Infected mice were monitored by observers blinded to the treatments for clinical signs of scrapie requiring euthanasia (A). Data are percentages of animals not euthanized versus days postinfection (Days). The day each individual mouse was euthanized, the median day of euthanasia for each mouse cohort, and the number of animals in each group are given in Table 4. Statistical analysis was performed using Mantel-Cox log rank analysis comparing PLX5622-treated to untreated animals. In addition, RML-infected mice were scored by observers blinded to the treatments for changes in severity of clinical presentation (scrapie severity score) (B) and nesting behavior (C) at various days postinfection (DPI). Severity of clinical presentation was scored from 0 to 3, where 0 represented no signs and 3 indicated signs requiring euthanasia, and nesting behavior was scored on a scale of 1 to 5, where 5 was a near-perfect nest and 1 was no nest (see Materials and Methods for details). All scores are representative of the average score of the study group at each day postinfection. Scrapie severity scoring stopped once the all-PLX5622-treatment group averaged a score of 3. Error bars represent the standard errors of the means. Multiple t test was performed comparing scrapie severity (B) and nesting scores (C) between PLX5622-treated and untreated groups of mice at specific time points using GraphPad software. Statistical significance was determined using the Holm-Sidak method to correct for multiple comparisons, with alpha of 0.05. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.