Somatostatin regulates the clock sensitivity to evening light.

Area of Science:

• Chronobiology
• Neuroendocrinology
• Molecular Biology

Background:

• Biological rhythms are synchronized to environmental cues like the light-dark cycle.
• The internal biological clock's entrainment is crucial for organismal adaptation.
• Somatostatin (SST) and its receptor SSTR1 play roles in physiological regulation.

Purpose of the Study:

• To investigate the role of somatostatin (SST) in regulating circadian clock responses to photoperiod.
• To elucidate the involvement of the somatostatin receptor 1 (SSTR1) in light sensitivity of the central clock.

Main Methods:

• Genetic deficiency models: somatostatin (SST) knockout mice and SSTR1 knockout mice.
• Pharmacological inhibition of SSTR1 and administration of an SSTR1 agonist (CH-275).
• Assessment of circadian activity phase under different photoperiodic conditions.
• Histological analysis of SSTR1 cell activation.

Main Results:

• SST-deficient mice exhibit a significant phase delay in activity under long photoperiods.
• This phase delay is replicated in SSTR1 knockout mice and with SSTR1 pharmacological inhibition.
• Histology confirms SST inhibits light-induced SSTR1 cell activation.
• SSTR1 agonist CH-275 treatment normalizes the circadian phase delay in SST-deficient mice.

Conclusions:

• The somatostatin-SSTR1 system plays an inhibitory role in the light sensitivity of the central circadian clock (SCN).
• This system is particularly important for regulating clock responses at dusk under long photoperiods.
• Findings offer insights into the molecular mechanisms governing circadian entrainment to light cycles.