Sleep disturbances in highly stress reactive mice: modeling endophenotypes of major depression.
Sleep disturbances in highly stress reactive mice: modeling endophenotypes of major depression.
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DOI：
10.1186/1471-2202-12-29
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发表时间：
2011-03-24
期刊：
影响因子：
2.4
通讯作者：
Yassouridis A
中科院分区：
文献类型：
--
作者：
Fenzl T;Touma C;Romanowski CP;Ruschel J;Holsboer F;Landgraf R;Kimura M;Yassouridis A
神经元机制的情感障碍，如抑郁症（MD）仍然知之甚少。通过选择性饲养小鼠的高（HR），中间（IR），或低（LR）的下丘脑-垂体-肾上腺皮质（HPA）轴的反应性，我们最近建立了一个新的遗传动物模型的极端应激反应（SR）。在行为、内分泌和神经生物学水平上表征该SR小鼠模型的研究揭示了与在MD患者中观察到的关键内表型的若干相似性。HR小鼠显示出节律性和睡眠测量（例如快速眼动睡眠（REMS）和非REM睡眠（NREMS））以及慢波活动的变化，表明睡眠功效降低和REMS增加。在本研究中，我们感兴趣的是，在多大程度上的几个脑电图（EEG）参数，包括相关频带的详细频谱分析，可以揭示进一步改变睡眠结构在这个动物模型。三个繁殖系中的每一个的八个成年雄性配备有硬膜外EEG和肌内肌电图（EMG）电极。恢复后，进行EEG和EMG记录两天。与IR和LR动物相比，HR小鼠的REMS和觉醒量以及警戒状态之间的转换次数存在差异。在HR动物中，从NREMS到REMS和从REMS到觉醒的转换频率增加在整个明-暗周期中是稳健的。详细的频谱EEG参数的统计分析表明，特别是在NREMS期间，theta（6-9 Hz），alpha（10-15 Hz）和eta（16-22.75 Hz）频带的功率在三个育种系之间存在显著差异。显著功率差异的明确定义的分布可以被分配到亮相和暗相期间的不同时间。特别是在NREMS期间，组间差异是稳健的，并且可以在明暗周期中连续监测。HR小鼠，即那些具有遗传倾向以响应压力而过度激活其HPA轴的动物，显示出睡眠结构的紊乱模式，类似于抑郁症患者的已知模式。在几个频段的EEG，这似乎也至少部分模仿临床观察的显着改变，建议SR小鼠线作为一个有前途的动物模型的基础研究机制的睡眠障碍在MD。
Neuronal mechanisms underlying affective disorders such as major depression (MD) are still poorly understood. By selectively breeding mice for high (HR), intermediate (IR), or low (LR) reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis, we recently established a new genetic animal model of extremes in stress reactivity (SR). Studies characterizing this SR mouse model on the behavioral, endocrine, and neurobiological levels revealed several similarities with key endophenotypes observed in MD patients. HR mice were shown to have changes in rhythmicity and sleep measures such as rapid eye movement sleep (REMS) and non-REM sleep (NREMS) as well as in slow wave activity, indicative of reduced sleep efficacy and increased REMS. In the present study we were interested in how far a detailed spectral analysis of several electroencephalogram (EEG) parameters, including relevant frequency bands, could reveal further alterations of sleep architecture in this animal model. Eight adult males of each of the three breeding lines were equipped with epidural EEG and intramuscular electromyogram (EMG) electrodes. After recovery, EEG and EMG recordings were performed for two days. Differences in the amount of REMS and wakefulness and in the number of transitions between vigilance states were found in HR mice, when compared with IR and LR animals. Increased frequencies of transitions from NREMS to REMS and from REMS to wakefulness in HR animals were robust across the light-dark cycle. Detailed statistical analyses of spectral EEG parameters showed that especially during NREMS the power of the theta (6-9 Hz), alpha (10-15 Hz) and eta (16-22.75 Hz) bands was significantly different between the three breeding lines. Well defined distributions of significant power differences could be assigned to different times during the light and the dark phase. Especially during NREMS, group differences were robust and could be continuously monitored across the light-dark cycle. The HR mice, i.e. those animals that have a genetic predisposition to hyper-activating their HPA axis in response to stressors, showed disturbed patterns in sleep architecture, similar to what is known from depressed patients. Significant alterations in several frequency bands of the EEG, which also seem to at least partly mimic clinical observations, suggest the SR mouse lines as a promising animal model for basic research of mechanisms underlying sleep impairments in MD.
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影响因子：
5.6
作者：
BONNET, MH;ARAND, DL
通讯作者：
ARAND, DL
DOI：
10.1073/pnas.1034823100
发表时间：
2003-05-13
影响因子：
11.1
作者：
El Yacoubi, M;Bouali, S;Vaugeois, JM
通讯作者：
Vaugeois, JM
影响因子：
11.3
作者：
Bearden, Carrie E.;Glahn, David C.;Soares, Jair C.
通讯作者：
Soares, Jair C.
影响因子：
3.5
作者：
Bale, Tracy L.
通讯作者：
Bale, Tracy L.
影响因子：
7.6
作者：
GILES, DE;JARRETT, RB;RUSH, AJ
通讯作者：
RUSH, AJ