Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer’s disease

PF-670462 lengthens the short circadian period defect in the APP-PS1 line and delays activity offset

We first assessed the baseline rhythmicity in APP-PS1 mice vs. nontransgenic (nTg) controls in 12:12 light dark cycles (LD) and in constant darkness (DD). We found no difference between genotypes in 12:12LD, but found a significantly shorter period in APP-PS1 mice (23.69 vs. 23.95; F(1,49) = 5.21, p < 0.01) in DD (Fig. 1A,B). In LD, there was a significant effect of drug treatment (F(2,48) = 4.10, p < 0.05) and an interaction between experimental phase and drug treatment (F(2,48) = 5.82, p < 0.01) on period, although only 30 mg/kg PF-670462 significantly lengthened the period (data not shown). There were also significant effects of genotype (F(1,49) = 4.21, p < 0.05), drug treatment (F(2,48) = 10.56, p < 0.05) and experimental phase…