Figure 6

Activation of CaMK4 β /CREB signaling in scrapie-infected mice early in disease. Targeted tertiary analyses of the NMDAR-regulated CaMK4β signaling pathway in brainstem-cerebellum, subcortical and cortical regions of scrapie-infected mice at 70, 90, 110, 130 dpi or at terminal stage of disease (TER; 155–190 dpi). (A) Levels of phosphorylated p38 (T180/Y182), Lyn (Y396), RSK1 (S380), nNOS (S847), CaMK4β (T196), and CREB (S133) in the brainstem-cerebellums of each of the three scrapie-infected mice at each time, normalized to those in the mock-infected mice, shown by color bars. The proteins in dashed lines were not analyzed. (B) Levels of phosphorylated CaMK4β (T196) and CREB (S133) in all macrodissected regions, normalized to those in the mock-infected mice, shown as time series. Mean ± SD; n = 3 (Mean ± range for CaMK4β (T196) at 90 dpi [subcortical region] and 110 dpi [brainstem-cerebellum], and CREB (S133) at 130 dpi [brainstem-cerebellum]; n = 2). Error bars on the x-axes, range in time of onset of terminal disease. The differences in phosphorylation levels in scrapie- versus mock-infected mice were analyzed by two-tailed paired ratio t-test. *P < 0.05; **P < 0.01.