Wang Yumeng, Paul Ketema N, Block Gene D, Deboer Tom, Colwell Christopher S
Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
bioRxiv. 2025 Mar 24:2025.03.22.644752. doi: 10.1101/2025.03.22.644752.
Epilepsy is one of the most common comorbidities in individuals with autism spectrum disorders (ASDs). Many patients with epilepsy as well as ASD experience disruptions in their sleep-wake cycle and exhibit daily rhythms in expression of symptoms. Chronic exposure to light at nighttime can disrupt sleep and circadian rhythms. Contactin associated protein-like 2 knockout ( KO) mice, a model for autism spectrum disorder (ASD) and epilepsy, exhibit sleep and circadian disturbances and seizure-like events. This study examines how chronic dim light at night (DLaN) exposure affects sleep architecture, EEG power spectra, and seizure activity in KO and wildtype (WT) mice. Using electroencephalography (EEG) recordings, male and female KO and WT mice were exposed to DLaN (5 lux) for 2 or 6 weeks. EEG recordings were analyzed to assess sleep architecture, power spectrum, and seizure-like events. DLaN exposure delays the wake onset and disrupts sleep patterns in a sex-dependent manner, with females being more affected. DLaN significantly increased slow-wave activity (SWA, 0.5-4 Hz) in both WT and KO mice, indicating increased sleep pressure. Finally, we found that DLaN dramatically increased the frequency of seizure-like events in the Cntnap2 KO mice and even increased the occurrence rate in the WT mice. Spectral analysis of seizure-like events revealed increased theta power, suggesting the involvement of hippocampus. Chronic DLaN exposure disrupts sleep and increases seizure-like events in KO mice, with sex-specific differences. These findings emphasize the potential risks of nighttime light exposure for individuals with ASD and epilepsy, reinforcing the need to manage light exposure to improve sleep quality and reduce seizure risk.
癫痫是自闭症谱系障碍(ASD)患者中最常见的共病之一。许多患有癫痫以及自闭症谱系障碍的患者的睡眠-觉醒周期会受到干扰,并且症状表现呈现出日节律性。夜间长期暴露于光线下会扰乱睡眠和昼夜节律。接触蛋白相关蛋白样2基因敲除(KO)小鼠是自闭症谱系障碍(ASD)和癫痫的一种模型,表现出睡眠和昼夜节律紊乱以及癫痫样发作事件。本研究探讨了夜间慢性暗光(DLaN)暴露如何影响KO小鼠和野生型(WT)小鼠的睡眠结构、脑电图功率谱和癫痫活动。通过脑电图(EEG)记录,将雄性和雌性KO小鼠和WT小鼠暴露于DLaN(5勒克斯)下2周或6周。对脑电图记录进行分析以评估睡眠结构、功率谱和癫痫样发作事件。DLaN暴露会延迟觉醒开始,并以性别依赖的方式扰乱睡眠模式,雌性受影响更大。DLaN显著增加了野生型和KO小鼠的慢波活动(SWA,0.5 - 4赫兹),表明睡眠压力增加。最后,我们发现DLaN显著增加了Cntnap2基因敲除小鼠癫痫样发作事件的频率,甚至增加了野生型小鼠的发生率。对癫痫样发作事件的频谱分析显示θ波功率增加,提示海马体参与其中。慢性DLaN暴露会扰乱KO小鼠的睡眠并增加癫痫样发作事件,存在性别特异性差异。这些发现强调了夜间光线暴露对自闭症谱系障碍和癫痫患者的潜在风险,强化了控制光线暴露以改善睡眠质量和降低癫痫风险的必要性。