Cui Xiang-Yu, Yang Guang, Cui Su-Ying, Cao Qing, Huang Yuan-Li, Ding Hui, Ye Hui, Zhang Xue-Qiong, Wang Zi-Jun, Zhang Yong-He
Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing, 100191, China.
Department of Pharmacology, Peking University, School of Basic Medical Science, Beijing, 100191, China.
Neurosci Lett. 2018 Aug 24;682:74-78. doi: 10.1016/j.neulet.2018.06.017. Epub 2018 Jun 9.
Repeated corticosterone (CORT) injections reliably produce depressive-like behavior in rodents. Our previous study showed that sleep parameters were altered in rats after daily injections of CORT for 7 days, and sleep disturbances appeared to be correlated with depressive-like behavior. The aim of the present study was to investigate time-dependent correlations between changes in sleep parameters and the formation of depressive-like behavior in rats after more prolonged treatment with CORT. Rats received daily injections of CORT (40 mg/kg, s.c.) for 7, 14, or 21 days. Electroencephalographic recordings were performed to study sleep parameters. The sucrose preference test and forced swim test were performed to evaluate depressive-like behavior. Western blot was used to detect protein levels. Our results showed that 7-day CORT treatment resulted in no significant depressive-like behavior or changes in rapid-eye-movement (REM) sleep. However, the duration of non-REM sleep significantly decreased, tyrosine hydroxylase (TH) levels significantly increased, and glucocorticoid receptor (GR) expression decreased in the locus coeruleus. Treatment with CORT for 14 and 21 days increased depressive-like behavior, enhanced REM sleep, shortened REM sleep latency, decreased TH and GR levels, and increased the levels of the chaperone FK506 binding protein 51 (FKBP51) in the locus coeruleus. These results indicate that the development of depression after chronic CORT treatment may be related to the formation of sleep disorders. Abnormalities of REM sleep may be a characteristic of sleep in models of depression that is induced by chronic CORT administration in rats. The noradrenergic system and GR pathway in the locus coeruleus may be involved in the formation of depression concomitant with sleep disturbances.
重复注射皮质酮（CORT）能可靠地在啮齿动物中产生类似抑郁的行为。我们之前的研究表明，每天注射CORT 7天后，大鼠的睡眠参数会发生改变，且睡眠障碍似乎与类似抑郁的行为相关。本研究的目的是探讨在大鼠接受更长时间的CORT治疗后，睡眠参数变化与类似抑郁行为形成之间的时间依赖性相关性。大鼠每天皮下注射CORT（40mg/kg），持续7、14或21天。通过脑电图记录来研究睡眠参数。进行蔗糖偏好试验和强迫游泳试验以评估类似抑郁的行为。采用蛋白质免疫印迹法检测蛋白质水平。我们的结果表明，7天的CORT治疗未导致明显的类似抑郁行为或快速眼动（REM）睡眠的变化。然而，非快速眼动睡眠的持续时间显著缩短，蓝斑中的酪氨酸羟化酶（TH）水平显著升高，糖皮质激素受体（GR）表达降低。14天和21天的CORT治疗增加了类似抑郁的行为，增强了REM睡眠，缩短了REM睡眠潜伏期，降低了TH和GR水平，并增加了蓝斑中伴侣蛋白FK506结合蛋白51（FKBP51）的水平。这些结果表明，慢性CORT治疗后抑郁症的发展可能与睡眠障碍的形成有关。REM睡眠异常可能是大鼠慢性CORT给药诱导的抑郁症模型中睡眠的一个特征。蓝斑中的去甲肾上腺素能系统和GR通路可能参与了伴随睡眠障碍的抑郁症的形成。
