Suppression of preoptic sleep-regulatory neuronal activity during corticotropin-releasing factor-induced sleep disturbance
Suppression of preoptic sleep-regulatory neuronal activity during corticotropin-releasing factor-induced sleep disturbance
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DOI：
10.1152/ajpregu.00176.2015
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发表时间：
2015-11-01
影响因子：
2.8
通讯作者：
Szymusiak, Ronald
中科院分区：
文献类型：
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作者：
Gvilia, Irma;Suntsova, Natalia;Szymusiak, Ronald
促肾上腺皮质激素释放因子（CRF）参与睡眠和觉醒调节。外源性CRF引起睡眠抑制，与至少两个重要的唤醒系统的激活相关：脑桥去甲肾上腺素能和下丘脑食欲素/下丘脑泌素神经元。目前尚不清楚CRF是否也影响促进睡眠的神经系统。我们假设CRF介导的觉醒和睡眠变化涉及位于视前区的下丘脑睡眠调节神经元的活性降低。为了验证这一假设，我们研究了在不同的实验条件下，脑室内注射CRF对睡眠-觉醒指标和正中视前核（MnPN）和腹外侧视前区（VLPO）GABA能神经元c-Fos表达的影响。在基线休息阶段给予CRF（0.1 nmol）导致睡眠开始延迟，非快速眼动（NREM）睡眠的总量和平均持续时间减少。在急性睡眠剥夺（SD）期间给予CRF导致恢复睡眠抑制和MnPN/VLPO GABA能神经元c-Fos表达减少。与溶剂对照组相比，脑室内CRF增强了暴露于种属特异性心理应激源（雄性同种动物的脏笼子）的大鼠的NREM和REM睡眠的干扰。在CRF处理组的脏笼暴露大鼠中，表达c-Fos的MnPN/VLPO GABA能神经元的数量减少。这些发现证实了CRF参与觉醒-睡眠周期调节，并表明大脑中增加的CRF信号传导1）对睡眠丧失的稳态反应产生负面影响，2）加剧应激诱导的睡眠障碍，3）抑制MnPN和VLPO的睡眠调节神经元的活性。
Corticotropin releasing factor (CRF) is implicated in sleep and arousal regulation. Exogenous CRF causes sleep suppression that is associated with activation of at least two important arousal systems: pontine noradrenergic and hypothalamic orexin/hypocretin neurons. It is not known whether CRF also impacts sleep-promoting neuronal systems. We hypothesized that CRF-mediated changes in wake and sleep involve decreased activity of hypothalamic sleep-regulatory neurons localized in the preoptic area. To test this hypothesis, we examined the effects of intracerebroventricular administration of CRF on sleep-wake measures and c-Fos expression in GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) in different experimental conditions. Administration of CRF (0.1 nmol) during baseline rest phase led to delayed sleep onset and decreases in total amount and mean duration of non-rapid eye movement (NREM) sleep. Administration of CRF during acute sleep deprivation (SD) resulted in suppression of recovery sleep and decreased c-Fos expression in MnPN/VLPO GABAergic neurons. Compared with vehicle controls, intracerebroventricular CRF potentiated disturbances of both NREM and REM sleep in rats exposed to a species-specific psychological stressor, the dirty cage of a male conspecific. The number of MnPN/VLPO GABAergic neurons expressing c-Fos was reduced in the CRF-treated group of dirty cage-exposed rats. These findings confirm the involvement of CRF in wake-sleep cycle regulation and suggest that increased CRF signaling in the brain 1) negatively affects homeostatic responses to sleep loss, 2) exacerbates stress-induced disturbances of sleep, and 3) suppresses the activity of sleep-regulatory neurons of the MnPN and VLPO.