Abstract：
Alteration of motor control during REM sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 is not associated with alpha-synucleinopathies. To determine whether the chronic absence of ORX neuropeptides is sufficient to induce RBD symptoms, we analyzed during REM sleep the EMG signal of the prepro-hypocretin knockout mice (ORX-/-), a recognized mouse model of NT1. Then, we evaluated the severity of motor alterations by comparing EMG data of ORX-/- mice to those of mice with a targeted suppression of the sublaterodorsal glutamatergic neurotransmission, a recognized rodent model of iRBD. We found a significant alteration of tonic and phasic components of EMG during REM sleep in ORX-/- mice, with more phasic events and more REM sleep episodes without atonia compared to the control wild-type mice. However, these phasic events were fewer, shorter and less complex in ORX-/- mice compared to the RBD-like ORX-/- mice. We thus show that ORX-deficiency, as seen in NT1, is sufficient to impair muscle atonia during REM sleep with a moderate severity of alteration as compared to isolated RBD mice. As described in NT1 patients, we report a major inter-individual variability in the severity and the frequency of RBD symptoms in ORX-deficient mice.
摘要：
在睡眠障碍中已经广泛描述了REM睡眠期间运动控制的改变。特别是在孤立的REM睡眠行为障碍（iRBD）和1型发作性睡病（NT1）中。NT1是由食欲素/降纤素（ORX）神经元的损失引起的。与iRBD不同，NT1的RBD共病症状与α-突触核蛋白病无关。为了确定ORX神经肽的慢性缺乏是否足以诱发RBD症状，我们在REM睡眠期间分析了前hypocretin基因敲除小鼠（ORX-/-）的EMG信号，公认的NT1小鼠模型。然后，我们通过比较ORX-/-小鼠的EMG数据与靶向抑制侧耳下谷氨酸能神经传递的小鼠的EMG数据来评估运动改变的严重程度，一种公认的iRBD啮齿动物模型。我们发现ORX-/-小鼠在REM睡眠过程中EMG的强直和相位成分发生了显着变化，与对照野生型小鼠相比，有更多的阶段性事件和更多的REM睡眠发作，而没有失去症。然而,这些阶段性事件较少，与RBD样ORX-/-小鼠相比，ORX-/-小鼠更短，更不复杂。因此，我们证明了ORX缺乏，如在NT1中所见，与分离的RBD小鼠相比，在REM睡眠期间足以损害肌肉无力，并具有中等严重程度的改变。如NT1患者所述，我们报告了ORX缺陷小鼠中RBD症状的严重程度和频率的主要个体间差异.
