A rodent model of traumatic stress induces lasting sleep and quantitative electroencephalographic disturbances.
A rodent model of traumatic stress induces lasting sleep and quantitative electroencephalographic disturbances.
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DOI：
10.1021/cn500342u
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发表时间：
2015-03-18
影响因子：
5
通讯作者：
Jones CK
中科院分区：
文献类型：
--
作者：
Nedelcovych MT;Gould RW;Zhan X;Bubser M;Gong X;Grannan M;Thompson AT;Ivarsson M;Lindsley CW;Conn PJ;Jones CK
过度觉醒和睡眠障碍是创伤后应激障碍（PTSD）常见的衰弱症状。PTSD患者在清醒以及快速眼动（REM）和非REM（NREM）睡眠期间也表现出定量脑电图（qEEG）功率谱的异常。选择性5-羟色胺再摄取抑制剂（SSRIs）是PTSD的一线药物治疗，可适度缓解PTSD患者的过度觉醒症状，但对睡眠-觉醒结构缺陷几乎没有影响。由于缺乏相关的动物模型，这些睡眠-觉醒结构缺陷的新疗法的开发受到限制。因此，本研究调查是否单一的长期压力（SPS），啮齿动物模型的创伤性应激，诱导PTSD样睡眠-觉醒和qEEG频谱功率异常，与中央5-羟色胺（5-HT）和神经肽Y（NPY）信号在大鼠的变化。大鼠被植入遥测记录装置，以连续测量SPS治疗前后的EEG。第二组大鼠用于测量SPS诱导的血浆皮质酮，5-HT利用率和NPY表达的变化，包括神经恐惧回路的大脑区域。SPS引起持续的NREM和REM睡眠失调，伴随着状态依赖性的改变，在qEEG功率谱指示皮层过度觉醒。这些变化与皮质酮受体辅伴侣FK 506结合蛋白51的急性诱导和杏仁核中5-HT利用和NPY表达的延迟减少相对应。SPS代表PTSD相关睡眠-觉醒和qEEG紊乱的临床前模型，已知神经递质系统的潜在改变可调节睡眠-觉醒结构和神经恐惧回路。
Hyperarousal and sleep disturbances are common, debilitating symptoms of post-traumatic stress disorder (PTSD). PTSD patients also exhibit abnormalities in quantitative electroencephalography (qEEG) power spectra during wake as well as rapid eye movement (REM) and non-REM (NREM) sleep. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for PTSD, provide modest remediation of the hyperarousal symptoms in PTSD patients, but have little to no effect on the sleep–wake architecture deficits. Development of novel therapeutics for these sleep–wake architecture deficits is limited by a lack of relevant animal models. Thus, the present study investigated whether single prolonged stress (SPS), a rodent model of traumatic stress, induces PTSD-like sleep–wake and qEEG spectral power abnormalities that correlate with changes in central serotonin (5-HT) and neuropeptide Y (NPY) signaling in rats. Rats were implanted with telemetric recording devices to continuously measure EEG before and after SPS treatment. A second cohort of rats was used to measure SPS-induced changes in plasma corticosterone, 5-HT utilization, and NPY expression in brain regions that comprise the neural fear circuitry. SPS caused sustained dysregulation of NREM and REM sleep, accompanied by state-dependent alterations in qEEG power spectra indicative of cortical hyperarousal. These changes corresponded with acute induction of the corticosterone receptor co-chaperone FK506-binding protein 51 and delayed reductions in 5-HT utilization and NPY expression in the amygdala. SPS represents a preclinical model of PTSD-related sleep–wake and qEEG disturbances with underlying alterations in neurotransmitter systems known to modulate both sleep–wake architecture and the neural fear circuitry.
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影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
7.4
作者：
Lee, HJ;Lee, MS;Paik, IH
通讯作者：
Paik, IH
影响因子：
2.9
作者：
GROENINK, L;VANDERGUGTEN, J;OLIVIER, B
通讯作者：
OLIVIER, B
DOI：
10.1176/appi.ajp.2012.12040432
发表时间：
2013-04
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Germain A
通讯作者：
Germain A
影响因子：
10.6
作者：
Levy-Gigi, Einat;Szabo, Csilla;Keri, Szabolcs
通讯作者：
Keri, Szabolcs