Antidepressant effect of blue light on depressive phenotype induced by the unfixed light pattern in mice

Shift work and social jetlag groups are at higher risk for depression, with the unfixed light pattern (ULP) potentially serving as one of critical risk factors. Evidence suggests that the ULP induces depressive phenotypes in rodents, possibly mediated by the circadian-orexinergic system. Blue light has been found to have a significant antidepressant effect in light therapy. This study explored the interventional effects of blue light on ULP-induced depressive phenotype of mice and the possible associations between the circadian-orexinergic system and depression. C57BL/6 J mice were exposed to ULP (alternating light-dark cycles every 6 days for 54 days) with or without 2-hour blue light supplementation. Behavioral tests (tail suspension test and forced swimming test) revealed that blue light significantly improved ULP-induced increase in immobilization time. Furthermore, blue light enhanced circadian entrainment efficiency, normalizing disrupted rhythms of circadian activity, serum corticosterone, melatonin, and hepatic clock genes. ULP-induced desynchronization of suprachiasmatic nucleus clock genes, alongside reduced levels of orexin-A(OX-A) in the lateral hypothalamus area and dorsal raphe nucleus (DRN), alongside decreased serotonin(5-HT) in the DRN, were significantly improved by blue light. This study shows that blue light prevents the ULP-induced depressive phenotype in mice, which may be associated with the restoration of circadian system entrainment and orexinergic system. These findings might provide new ideas for intervention and prevention of shift work and social jetlag-related depression.