PDF(Pubmed)
Abstract：
UNASSIGNED: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.
UNASSIGNED: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
UNASSIGNED: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
UNASSIGNED: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
UNASSIGNED: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
UNASSIGNED: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
UNASSIGNED: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
UNASSIGNED: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
UNASSIGNED: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
摘要：
■N-乙基马来酰亚胺（NEM），氯化钾共转运蛋白2（KCC2）受体的激动剂，与神经抑制结果相关，包括减少疼痛感知和预防癫痫发作。然而，其与睡眠诱导效应的关系仍未报道。
■本研究旨在研究NEM对阿普唑仑（Alp）睡眠诱导特性的潜在增强作用。
■使用正正反射的测试来鉴定Alp和NEM在小鼠中诱导睡眠促进作用的适当浓度。通过EEG/EMG分析评估总睡眠时间和睡眠质量。使用免疫荧光通过大脑中的c-fos免疫反应性检查了促进睡眠作用的神经机制。此外，Alp和NEM组合的潜在CNS副作用使用LABORAS自动家庭笼行为表型分析进行评估.
与单独施用1.84mg/kgAlp相比,联合施用Alp(1.84mg/kg)和NEM(1.0mg/kg)显著降低睡眠潜伏期并增加睡眠持续时间。这种效应的特征在于REM持续时间的显著增加。c-fos免疫反应性的发现表明，NEM可显着抑制与觉醒相关的大脑区域的神经元激活。此外,Alp和NEM的联合给药在自动家笼监测过程中对小鼠的神经行为没有影响。
■这项研究首次提出并证明了一种涉及Alp和NEM的联合疗法，不仅可以增强催眠作用，而且可以减轻潜在的中枢神经系统副作用。提示其在治疗失眠方面的潜在应用。
■本研究旨在研究NEM对阿普唑仑（Alp）睡眠诱导特性的潜在增强作用。
■使用正正反射的测试来鉴定Alp和NEM在小鼠中诱导睡眠促进作用的适当浓度。通过EEG/EMG分析评估总睡眠时间和睡眠质量。使用免疫荧光通过大脑中的c-fos免疫反应性检查了促进睡眠作用的神经机制。此外，Alp和NEM组合的潜在CNS副作用使用LABORAS自动家庭笼行为表型分析进行评估.
与单独施用1.84mg/kgAlp相比,联合施用Alp(1.84mg/kg)和NEM(1.0mg/kg)显著降低睡眠潜伏期并增加睡眠持续时间。这种效应的特征在于REM持续时间的显著增加。c-fos免疫反应性的发现表明，NEM可显着抑制与觉醒相关的大脑区域的神经元激活。此外,Alp和NEM的联合给药在自动家笼监测过程中对小鼠的神经行为没有影响。
■这项研究首次提出并证明了一种涉及Alp和NEM的联合疗法，不仅可以增强催眠作用，而且可以减轻潜在的中枢神经系统副作用。提示其在治疗失眠方面的潜在应用。
