Ficiarà Eleonora, Faniyan Oluwatomisin O, Simayi Reyila, Del Gallo Federico, Roberto Marisa, Ciccocioppo Roberto, Bellesi Michele, de Vivo Luisa
School of Pharmacy, University of Camerino, Italy.
Center for Neuroscience, University of Camerino.
PLoS One. 2025 May 29;20(5):e0324459. doi: 10.1371/journal.pone.0324459. eCollection 2025.
Alcohol use disorders (AUD) are bidirectionally associated with significant sleep disturbances, yet the underlying neural mechanisms remain poorly understood. The Marchigian Sardinian alcohol Preferring (msP) rat is a validated preclinical model that mirrors several genetic and behavioral traits of patients with AUD. This study aimed to characterize the sleep-wake architecture and EEG spectral activity in naïve msP rats compared to Wistar controls. We performed 24-hour polysomnography recordings, revealing that male msP rats (n = 9) spent 7.5% more time awake and less time in NREM sleep relative to Wistar rats (n = 9). This was accompanied by a more fragmented sleep-wake pattern, with a higher number of waking and sleep episodes, state transitions, and sleep fragmentation index. Spectral analysis demonstrated lower high-frequency power, with significant reductions in sigma and beta power during NREM sleep and increased theta/beta ratios during wakefulness. Slow-wave activity, an indicator of sleep pressure, showed a blunted rise and fall across the sleep cycle in msP rats, with reduced amplitude and slope of slow waves during early sleep. Moreover, msP rats exhibited decreased spindle activity, with significantly lower spindle incidence, amplitude, and duration. These findings suggest that msP rats display significant sleep disturbances, including disrupted NREM sleep and altered spectral characteristics in brain activity that partially resemble changes reported in individuals with AUD. This altered sleep profile may reflect neural circuit dysfunctions linked to substance use vulnerability, offering potential insights into the neurobiological basis of sleep disturbances in these complex neuropsychiatric disorders.
酒精使用障碍（AUD）与严重的睡眠障碍存在双向关联，但其潜在的神经机制仍知之甚少。马尔基安撒丁岛嗜酒（msP）大鼠是一种经过验证的临床前模型，反映了AUD患者的几种遗传和行为特征。本研究旨在比较初发msP大鼠与Wistar对照大鼠的睡眠-觉醒结构和脑电图频谱活动。我们进行了24小时多导睡眠图记录，发现雄性msP大鼠（n = 9）相对于Wistar大鼠（n = 9），清醒时间多花了7.5%，非快速眼动睡眠（NREM）时间更少。这伴随着更碎片化的睡眠-觉醒模式，有更多的清醒和睡眠时段、状态转换以及睡眠碎片化指数。频谱分析显示高频功率较低，在NREM睡眠期间西格玛和贝塔功率显著降低，而在清醒期间θ/贝塔比率增加。慢波活动是睡眠压力的一个指标，在msP大鼠的睡眠周期中其上升和下降较为平缓，早期睡眠期间慢波的振幅和斜率降低。此外，msP大鼠的纺锤波活动减少，纺锤波发生率、振幅和持续时间显著降低。这些发现表明，msP大鼠表现出明显的睡眠障碍，包括NREM睡眠紊乱和大脑活动频谱特征改变，部分类似于AUD患者报告的变化。这种改变的睡眠模式可能反映了与物质使用易感性相关的神经回路功能障碍，为这些复杂神经精神疾病中睡眠障碍的神经生物学基础提供了潜在的见解。
