Monaca Christelle, Laloux Charlotte, Jacquesson Jean-Marie, Gelé Patrick, Maréchal Xavier, Bordet Régis, Destée Alain, Derambure Philippe
Service de Neurophysiologie Clinique, EA2683, Hôpital R. Salengro, CHRU de Lille, F-59037 Lille cedex, France.
Eur J Neurosci. 2004 Nov;20(9):2474-8. doi: 10.1111/j.1460-9568.2004.03694.x.
Sleep disturbances and vigilance disorders are frequently observed in Parkinson's disease. Despite the fact that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse is one of the best-known animal models of Parkinson's disease, sleep analysis has never previously been performed in this system. In the present study, we explored sleep-wakefulness cycles in MPTP-treated mice and compared the results to data from untreated mice. MPTP (25 mg/kg) was injected daily for 5 days. After recovery, polysomnography was recorded over 48 h. Dopaminergic lesions of the substantia nigra and striata were evaluated using immunohistochemical markers. Immunohistochemical analysis showed a loss of dopaminergic neurons in MPTP mice. Compared with controls, MPTP-treated mice presented changes in sleep architecture throughout the nycthemeral period, with longer wakefulness and paradoxical sleep episodes and an increase in the amount of paradoxical sleep. We observed changes in sleep architecture in MPTP-treated mice, compared with saline-treated mice. MPTP mice show more consolidated vigilance states with higher amount of paradoxical sleep than controls. Although the MPTP-treated mouse is not a good model of sleep disturbances in PD, our results suggest that it could be a good pharmacological model for studying the effects of dopaminergic treatments on animal sleep-wakefulness cycles.
睡眠障碍和警觉性障碍在帕金森病中经常出现。尽管1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠是最著名的帕金森病动物模型之一，但此前从未在该模型系统中进行过睡眠分析。在本研究中，我们探究了MPTP处理小鼠的睡眠-觉醒周期，并将结果与未处理小鼠的数据进行了比较。连续5天每天注射MPTP（25mg/kg）。恢复后，记录48小时的多导睡眠图。使用免疫组化标记物评估黑质和纹状体的多巴胺能损伤。免疫组化分析显示MPTP小鼠中多巴胺能神经元减少。与对照组相比，MPTP处理的小鼠在整个昼夜周期的睡眠结构发生了变化，清醒时间和异相睡眠期延长，异相睡眠量增加。与生理盐水处理的小鼠相比，我们观察到MPTP处理的小鼠睡眠结构发生了变化。MPTP小鼠比对照组表现出更稳定的警觉状态，异相睡眠量更高。虽然MPTP处理的小鼠不是帕金森病睡眠障碍的良好模型，但我们的结果表明，它可能是研究多巴胺能治疗对动物睡眠-觉醒周期影响的良好药理学模型。
