Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson's disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.

中文翻译：

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全天候急性左旋多巴给药可改善半帕金森氏病大鼠的REM睡眠，而无无心律失常。

快速眼动运动（REM）睡眠无心律失常（RSWA）是REM睡眠行为障碍（RBD）的标志，通常与帕金森氏病（PD）并存。尽管啮齿动物模型通常用于研究PD，但对RBD的神经生物学和行为相关性仍然知之甚少。因此，我们开发了基于行为的标准，以在PD的半帕金森病大鼠模型中识别RSWA。对大鼠的录像进行了分析，以开发出一种标准，该标准包括在多导睡眠图确认的睡眠清醒阶段期间发生的行为体征。睡眠懒散（仅由重力引起的身体或头部的姿势移动）被确定为REM睡眠发作的独特行为标志，并且在RSWA期间在半帕金森病大鼠中发生了改变。对照的所有睡眠-觉醒阶段的基于行为的标准与多导睡眠图之间存在显着相关性，但半帕金森氏大鼠则没有，表明帕金森氏症的睡眠-觉醒结构恶化。然后，我们使用间歇性和​​全天候（ATC）给药方案测试了左旋多巴在改善RSWA中的功效。通过多导睡眠图和基于行为的标准测量，ATC左旋多巴的4 mg / kg剂量给药48 h导致RSWA显着降低，并且前肢运动功能障碍得到改善。我们的发现表明，在半帕金森病大鼠模型中可以可靠地表征RSWA的现象学相关性。ATC左旋多巴的使用改善了该模型中的RSWA，而没有对整体睡眠-唤醒结构和帕金森氏运动缺陷的治疗益处产生有害影响。这些发现表明，进一步的研究可能允许应用类似的方法来治疗PD患者的RBD。