Altered responsiveness to photic stimuli contribute to circadian disruption in cystic fibrosis.

BACKGROUND

People with cystic fibrosis (pwCF) and animal models show evidence of disrupted circadian rhythms (CR). CRs are controlled by light sensitive neurons of the suprachiasmatic nucleus (SCN). Characterizing how the CF SCN responds to light will inform mechanisms behind CR disruption and help to inform CR based treatments to mitigate CF symptoms exacerbated by circadian disruption.

METHODS

Mice were entrained and subsequently exposed to a 30 min light pulse one hour after usual lights out. The magnitude of the resulting phase delay in subsequent activity onset and molecular correlates of photic input at the SCN were then compared between CF and WT mice.

RESULTS

Light induced phase delays of activity onset in CF mice were reduced compared to WT controls. Reduced behavioral responses were also associated with altered molecular responses in the SCN, including attenuated cFOS levels in CF vs WT SCN. Data show that phosphorylation of ribosomal protein 6 (pS6) is reduced in CF, while targets down stream of 4E-BP1 such as vasoactive intestinal polypeptide levels (VIP) appear the same between genotypes.

CONCLUSIONS

Behavioral and molecular responses to a light pulse differ between CF and WT mice. Together these data suggest that similar photic input from the retina is being received by the SCN of CF and WT mice, but the mounted intracellular response to that photic input differs in CF. Investigation into these differences will be integral to understanding circadian disruption in CF and informing future intervention for CF symptoms known to be exacerbated by circadian disruption.