Glucocorticoid receptor in locus coeruleus mediates the repetitive treatment of corticosterone‐induced sleep disorders (656.6)

Abstract

Constantly increased cortisol level resulted from stress can cause serious physical or psychological disorders, but the mechanism of stress‐induced sleep disorders remains unclear. Here we described a novel model, which enables us to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). Rats were treated with CORT for 7 days and the sleep parameters were assessed by EEG. In this model, we observed significant decrease in total sleep time and increase in REM sleep time. Meanwhile, the glucocorticoid receptor(GR) level was notably lowered in Locus coeruleus(LC). We also observed the activation of noradrenergic neurons in LC and the suppression of GABAergic neurons activity in ventrolateral preoptic area(VLPO). Otherwise, no significant changes were found in other sleep regulating nuclei. In addition, we observed remarkable increase of NE in LC, VLPO and hypothalamus and increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO. Microinjection of GR antagonist, RU486 into LC reversed the sleep changes. These results suggested that GR in LC may play a role in the stress mimicked sleep disorders and support the hypothesis that the repetitive treatment of CORT may lower the GR level and induce the activation of noradrenergic neurons in LC, then inhibit GABAergic neurons in VLPO and consequently induced sleep disorders.Grant Funding Source: Supported by National Natural Science Foundation of China (No. 81173031, 81202511 and 81302746)