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Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment
Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371174/ https://www.ncbi.nlm.nih.gov/pubmed/25801728 http://dx.doi.org/10.1038/srep09442 |
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author | Wang, Zi-Jun Zhang, Xue-Qiong Cui, Xiang-Yu Cui, Su-Ying Yu, Bin Sheng, Zhao-Fu Li, Sheng-Jie Cao, Qing Huang, Yuan-Li Xu, Ya-Ping Zhang, Yong-He |
author_facet | Wang, Zi-Jun Zhang, Xue-Qiong Cui, Xiang-Yu Cui, Su-Ying Yu, Bin Sheng, Zhao-Fu Li, Sheng-Jie Cao, Qing Huang, Yuan-Li Xu, Ya-Ping Zhang, Yong-He |
author_sort | Wang, Zi-Jun |
collection | PubMed |
description | Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation. |
format | Online Article Text |
id | pubmed-4371174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43711742015-04-06 Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment Wang, Zi-Jun Zhang, Xue-Qiong Cui, Xiang-Yu Cui, Su-Ying Yu, Bin Sheng, Zhao-Fu Li, Sheng-Jie Cao, Qing Huang, Yuan-Li Xu, Ya-Ping Zhang, Yong-He Sci Rep Article Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation. Nature Publishing Group 2015-03-24 /pmc/articles/PMC4371174/ /pubmed/25801728 http://dx.doi.org/10.1038/srep09442 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Zi-Jun Zhang, Xue-Qiong Cui, Xiang-Yu Cui, Su-Ying Yu, Bin Sheng, Zhao-Fu Li, Sheng-Jie Cao, Qing Huang, Yuan-Li Xu, Ya-Ping Zhang, Yong-He Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title | Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title_full | Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title_fullStr | Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title_full_unstemmed | Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title_short | Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
title_sort | glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371174/ https://www.ncbi.nlm.nih.gov/pubmed/25801728 http://dx.doi.org/10.1038/srep09442 |
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