Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice

Light pollution has become a potential health risk factor worldwide. Chronic exposure to constant light (CCL) leads to depressive-like behavior, yet the mechanism remains unclear. In this study, mice exposed to CCL for 3 weeks exhibited depression-like behaviors, with decreased melatonin in plasma and increased oxidative stress in hippocampus. Meanwhile, CCL-exposed mice showed elevated plasma corticosterone (CORT) levels and diminished glucocorticoid receptor (GR) phosphorylation in hippocampus. Concurrently, glycogen synthase kinase 3 beta (GSK38) was inactivated with increased phosphorylation at Ser9. The interrelationship of GSK38 and GR was clarified in mouse hippocampal neuron (HT-22) cells. GSK38 inhibitor CHIR-99021 induced GR inhibition with diminished phosphorylation, while GR inhibitor RU486 did not affect GSK38 expression or phosphorylation. Furthermore, GSK38-mediated GR inhibition was reproduced in vitro in HT-22 cells treated with melatonin receptor antagonist luzindole and H2O2 in combination. Finally, melatonin reversed GSK38-mediated GR inhibition in hippocampus and improved CCL-induced depression-like behavior in mice. These results indicate that CCL induces melatonin deficiency and oxidative stress in hippocampus, which in turn leads to GSK38-mediated GR inhibition and depression-like behavior in mice.

Automated summary

The study found that chronic exposure to constant light leads to depression-like behavior in mice, possibly due to decreased melatonin and increased oxidative stress, which in turn results in GSK38-mediated GR inhibition affecting the emotional state of mice.