期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 228, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.112979
关键词
Chronic constant light; Melatonin; Oxidative stress; GSK38; GR; Hippocampus
资金
- National Key Research and Development Program of China [2016YFD0500502]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX18_0716]
- Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality, and Safety Control
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.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据