Fig. 4: Treatment with polyphenols attenuates anxiety but not IL-1β production induced by disruption of the circadian clock.

Analysis of behavior of wild-type and Bmal1^-/- mice tested in the dark-light box and elevated plus maze task. (A) Timeline of behavioral studies. (B-D) Time spent in the light zone (B), Entries into the light zone (C), and total distance traveled in the dark-light box task (D). (E–G) Time spent in the open arms (E), Entries into the open arms (F), and total distance traveled in the elevated plus maze task (G). N = 5–11 mice/group. (H) IL-1β production in the hippocampus and cortex. N = 3–10 mice per group. (I) mRNA expression of the inflammation-related genes IL1b, Nlrp3, and Hmgb1 in the hippocampus. (J) mRNA expression of the circadian clock genes Clock, Cry1, and Nr1d1 in the hippocampus. N = 3–10 mice/group. (K) Representative fluorescent images of CA1 hippocampal microglia. Red: Iba1. Green: Soma. Yellow: Branches. Scale bar: 15 μm. (L–N) Numbers (L), total branch length per cell (M), and total branch endpoints per cell (N) of hippocampal microglia. N = 3–5 mice/group, >4 hippocampal sections studied per animal. For anatomical studies, >25 cells studied per section. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by Two-Way ANOVA with Tukey’s post-test.