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 a...

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Autores principales:	Yang Yang, Wenduo Jiang, Yue Feng, Jie Liu, Hongwu Chen, Deyun Wang, Ruqian Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Chronic constant light Melatonin Oxidative stress GSK3β GR Hippocampus Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/0281df12b89d4991ab24e56430065283
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spelling	oai:doaj.org-article:0281df12b89d4991ab24e564300652832021-11-18T04:43:15ZMelatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice0147-651310.1016/j.ecoenv.2021.112979https://doaj.org/article/0281df12b89d4991ab24e564300652832021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321010915https://doaj.org/toc/0147-6513Light 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 (GSK3β) was inactivated with increased phosphorylation at Ser9. The interrelationship of GSK3β and GR was clarified in mouse hippocampal neuron (HT-22) cells. GSK3β inhibitor CHIR-99021 induced GR inhibition with diminished phosphorylation, while GR inhibitor RU486 did not affect GSK3β expression or phosphorylation. Furthermore, GSK3β-mediated GR inhibition was reproduced in vitro in HT-22 cells treated with melatonin receptor antagonist luzindole and H2O2 in combination. Finally, melatonin reversed GSK3β-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 GSK3β-mediated GR inhibition and depression-like behavior in mice.Yang YangWenduo JiangYue FengJie LiuHongwu ChenDeyun WangRuqian ZhaoElsevierarticleChronic constant lightMelatoninOxidative stressGSK3βGRHippocampusEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 112979- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chronic constant light Melatonin Oxidative stress GSK3β GR Hippocampus Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Chronic constant light Melatonin Oxidative stress GSK3β GR Hippocampus Environmental pollution TD172-193.5 Environmental sciences GE1-350 Yang Yang Wenduo Jiang Yue Feng Jie Liu Hongwu Chen Deyun Wang Ruqian Zhao Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
description	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 (GSK3β) was inactivated with increased phosphorylation at Ser9. The interrelationship of GSK3β and GR was clarified in mouse hippocampal neuron (HT-22) cells. GSK3β inhibitor CHIR-99021 induced GR inhibition with diminished phosphorylation, while GR inhibitor RU486 did not affect GSK3β expression or phosphorylation. Furthermore, GSK3β-mediated GR inhibition was reproduced in vitro in HT-22 cells treated with melatonin receptor antagonist luzindole and H2O2 in combination. Finally, melatonin reversed GSK3β-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 GSK3β-mediated GR inhibition and depression-like behavior in mice.
format	article
author	Yang Yang Wenduo Jiang Yue Feng Jie Liu Hongwu Chen Deyun Wang Ruqian Zhao
author_facet	Yang Yang Wenduo Jiang Yue Feng Jie Liu Hongwu Chen Deyun Wang Ruqian Zhao
author_sort	Yang Yang
title	Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
title_short	Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
title_full	Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
title_fullStr	Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
title_full_unstemmed	Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice
title_sort	melatonin alleviates hippocampal gr inhibition and depression-like behavior induced by constant light exposure in mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/0281df12b89d4991ab24e56430065283
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Melatonin alleviates hippocampal GR inhibition and depression-like behavior induced by constant light exposure in mice

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