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. 2019 Jul 8;15(7):e8838. doi: 10.15252/msb.20198838

Figure 1. Light attenuates the effect of PF‐670 more strongly in diurnal NHPs than in nocturnal mice.

Figure 1

  • A
    PF‐670 inhibits the phosphorylation of PER by CK1δ/ε (i) and delays the circadian phase, which is counterbalanced by light (ii). Thus, daily dosing leads to continually accumulating phase delay in DD and constant stable phase delay in LD.
  • B
    Measured free PF‐670 exposure in the brain tissue of mice and NHPs. Drug exposure in NHPs after administration of 10 mpk PF‐670 (AUC = 3.6 μM·h) is ˜7‐fold higher than that in mice given 32 mpk PF‐670 (AUC = 0.5 μM·h) (n = 2–3; mean ± SEM). The mouse data are adopted from (Kim et al, 2013).
  • C, D
    Double‐plotted actograms of NHPs’ activity for 16 days. NHPs were treated with 10 mpk PF‐670 for 3 consecutive days at the same solar time of day: 4 pm for the DD experiment (C) and 4:30 pm (ZT11) for the LD experiment (D), respectively, which are highlighted as red lines. White and black rectangles indicate the times of light going on and off (LD 12:12).
  • E, F
    Phase delay induced by the 3‐day dosing under DD (E) or LD (F). The phase of activity onset in NHPs (10 mpk) is more delayed than that in mice (32 mpk) under DD (E), but not under LD (F) (n = 3–8; = 0.03, one‐way analysis of variance (ANOVA); n.s., no significant difference). Veh denotes vehicle. The error bars represent mean ± SEM. The mouse data are adopted from (Kim et al, 2013).
  • G
    The quantification of (E) and (F) indicates that light has a stronger attenuating effect on the PF‐670‐induced phase delay in NHPs than in mice (n = 5–8; mean ± SEM; = 0.036, two‐way ANOVA).