title: Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment.
abstract: 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.
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Zi-Jun
authors: ZJ
authors: Wang
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Xue-Qiong
authors: XQ
authors: Zhang
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Xiang-Yu
authors: XY
authors: Cui
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Su-Ying
authors: SY
authors: Cui
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Bin
authors: B
authors: Yu
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Zhao-Fu
authors: ZF
authors: Sheng
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Sheng-Jie
authors: SJ
authors: Li
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Qing
authors: Q
authors: Cao
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Yuan-Li
authors: YL
authors: Huang
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Ya-Ping
authors: YP
authors: Xu
authors: Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing 100191, China.
authors: Yong-He
authors: YH
authors: Zhang
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects / Q000473:pathology; D000818:Animals; D003345:Corticosterone / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D015735:Mifepristone / Q000008:administration & dosage; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone