rPrPSc accumulation in neocortical synaptosomes coincide with increased amounts of NICD and translocation of NICD to neuronal nuclei. A. Kinetics of the log of neocortical rPrPSc accumulation in synaptosomes (open squares) relative to NICD concentration (filled circles). NICD levels in age matched PBS-inoculated mice are shown as controls (open circles). B. In control mice, confocal microscopy shows small amounts of NICD mostly in the cytoplasm in uninfected neocortical neurons. C. Confocal microscopy shows accumulation of NICD in the nuclei of cortical neurons in RML infected mice at 140 dpi. NICD (green) is detected by Notch-1 Val-1744 antibody from Cell Signaling Technology and the neuron specific antibody anti-NeuN (red) is from Chemicon. In A, data points are calculated from three independent experiments. ** P < 0.005; *** P < 0.0001 by Student's t test. Adapted from Ishikura et al. .