Fig. 1

Prion propagation in the limbic regions during disease. a An illustration of reduced nesting and mood disorder-like symptoms in a mouse with prion disease (middle, right) compared with a normal healthy mouse (left). b A schematic diagram illustrating the timeline of the study, where weanling wild-type mice were inoculated with RML prions, and ex vivo fresh coronal slices of the limbic regions (hippocampus, hypothalamus, amygdala) were used for the assessments in this study at a pre-clinical stage or mid-incubation period (50% of the disease progression to terminal stage disease at ~ 80 days post-inoculation, dpi) and at clinical onset (~ 70% of disease progression or at ~ 108 dpi). c Prion seeding activity (logSD50) in the limbic regions at the pre-clinical and clinical onset (Unpaired Student’s t-test was used to compare prion seeding activity between two disease time points within a region). d Western blotting for PrP (6D11 antibody) after an ultracentrifugation separation of soluble from insoluble isoforms, relative to the total PrP, in the three limbic regions in samples from uninfected controls (UN) and the two disease time points. The bottom panels are Coomassie stains of total protein for the total PrP blots. Molecular weight markers are on the right. e The quantification of the blots in d. PrP at each time point was compared to the UN control by unpaired Student’s t-test. c, e Each dot represents a mouse, and data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001