Skip to main content
[Preprint]. 2024 Apr 30:rs.3.rs-4331810. [Version 1] doi: 10.21203/rs.3.rs-4331810/v1

Figure 3: Small molecule ligands targeting REV-ERBs and RORs have distinct effects on circadian rhythms.

Figure 3:

Using IMHN expressing the Per2-luc reporter, circadian rhythms were evaluated for effects on amplitude using four distinct drug treatments that each target nuclear receptors involved in regulating circadian rhythms in different ways. A) The REV-ERB agonist GSK4112 showed concentration-dependent effects on rhythms with no significant effect at 1 μM, but a significant increase in amplitude at 10 μM. B) The REV-ERB antagonist showed no significant effect at 10 μM, but a significant decrease in amplitude at 20 μM. C) The ROR agonist SR1078 showed concentration-dependent effects on rhythms with no significant effect at 2 μM, but a significant amplitude decrease at 10 μM. D) The ROR inverse agonist SR1001 had no significant effect on rhythms at either of the concentrations tested (2 μM and 10 μM). All analyses were conducted using one-way ANOVA with post-tests to identify differences between groups (n= 4–12/group). Statistical significance was determined using p<0.05 indicated by *. Data shown in E-H are representative traces of vehicle (black) and drug-treated (blue) IMHNs, observed over a 5-day recording period. To emphasize the rhythmic component of the light emission signal, data were baseline subtracted using a detrended running average.