Progressive sleep and electroencephalogram changes in mice carrying the Huntington's disease mutation
Progressive sleep and electroencephalogram changes in mice carrying the Huntington's disease mutation
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DOI：
10.1093/brain/awt128
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发表时间：
2013-07-01
期刊：
影响因子：
14.5
通讯作者：
Morton, A. Jennifer
中科院分区：
文献类型：
--
作者：
Kantor, Sandor;Szabo, Lajos;Morton, A. Jennifer
亨廷顿病的睡眠障碍可能对患者的认知表现、情感行为和总体健康有害，但对亨廷顿病的睡眠和脑电图变化进展的全面描述从未进行过。在这里，我们研究了亨廷顿病转基因小鼠模型（R6/2小鼠）的睡眠和脑电图紊乱。我们将10只R6/2小鼠和5只野生型同窝小鼠植入肌电图电极、额额叶和额顶叶脑电图电极，然后记录症状前、症状期和疾病晚期的睡眠/觉醒行为。除了睡眠-觉醒评分外，我们还对睡眠脑电图进行了频谱分析。我们发现R6/2小鼠在9周龄时（症状前阶段）的睡眠和脑电图已经明显中断。当出现症状时，R6/2小鼠无法维持长时间的清醒，并且快速眼动睡眠的倾向增加。此外，θ波节律的峰值频率在快速眼动睡眠期间逐渐从7 Hz移动到6 Hz，而慢波活动在非快速眼动睡眠期间逐渐减少。最后，随着疾病的进展，在R6/2小鼠中出现异常的脑电图γ活动（30-40 Hz），而与睡眠状态无关。这让人想起精神分裂症患者在睡眠和精神病事件中描述的伽马功率增加。更好地了解亨廷顿病患者的睡眠和脑电图变化应该是一个优先事项，因为它将使临床医生能够启动适当的调查，并鼓励治疗，可以显着改善患者的生活质量。
Sleep disturbances in Huntington's disease may be deleterious to the cognitive performance, affective behaviour, and general well-being of patients, but a comprehensive description of the progression of changes in sleep and electroencephalogram in Huntington's disease has never been conducted. Here we studied sleep and electroencephalogram disturbances in a transgenic mouse model of Huntington's disease (R6/2 mice). We implanted 10 R6/2 mice and five wild-type littermates with electromyography electrodes, frontofrontal and frontoparietal electroencephalogram electrodes and then recorded sleep/wake behaviour at presymptomatic, symptomatic and late stages of the disease. In addition to sleep-wake scoring, we performed a spectral analysis of the sleep electroencephalogram. We found that sleep and electroencephalogram were already significantly disrupted in R6/2 mice at 9 weeks of age (presymptomatic stage). By the time they were symptomatic, R6/2 mice were unable to maintain long periods of wakefulness and had an increased propensity for rapid eye movement sleep. In addition, the peak frequency of theta rhythm was shifted progressively from 7 Hz to 6 Hz during rapid eye movement sleep, whereas slow wave activity decreased gradually during non-rapid eye movement sleep. Finally, as the disease progressed, an abnormal electroencephalogram gamma activity (30-40 Hz) emerged in R6/2 mice irrespective of sleep states. This is reminiscent of the increased gamma power described in schizophrenic patients during sleep and events of psychosis. Gaining a better understanding of sleep and electroencephalogram changes in patients with Huntington's disease should be a priority, since it will enable clinicians to initiate appropriate investigations and to instigate treatments that could dramatically improve patients' quality of life.