Type I interferon protects neurons from prions in in vivo models

Ishibashi, Daisuke; Homma, Takujiro; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Satoh, Katsuya; Mori, Tsuyoshi; Atarashi, Ryuichiro; Nishida, Noriyuki

NPRs may show medical efficacy in peripheral areas such as the spleen, resulting in delayed PrP Sc synthesis and accumulation in the brain. However, it remains to be clarified whether NPR acts in the brain. In our experiments, RO8191 was detected in high concentration in the brain and spleen of prion-infected mice at 100 dpi and at terminal Survival curves for the vehicle and RO8191-treated mice after inoculation intracerebrally (i.c.) with a 10 À1 dilution of 22 L-brain homogenate (P 5 0.05, log-rank test). PrP Sc levels (B) and histological changes (C) in the brain (cortex, Cx) and spleen are shown at 100 dpi and in the terminal phase of prion infection. (D) Lesion profiles in the same five brain regions are similar to those shown in Fig. 4 . Circle and triangle symbols indicate vehicle and RO8191-treated mice, respectively, at 100 dpi (black) and in the terminal stage (red). *P 5 0.05 and **P 5 0.01 versus vehicle mice at 100 dpi. Error bars represent SEM. Statistical significance was determined using an unpaired Student's t-test (B and D). These results represent at least three independent experiments.