Cerebrospinal fluid (CSF) flow through the brain parenchyma is facilitated by the astrocytic water channel aquaporin 4 (AQP4). Homeostatically regulated electroencephalographic (EEG) slow waves are a hallmark of deep non-rapid eye movement (NREM) sleep and have been implicated in the regulation of parenchymal CSF flow and brain clearance. The human AQP4 gene harbors several single nucleotide polymorphisms (SNPs) associated with AQP4 expression, brain-water homeostasis, and neurodegenerative diseases. To date, their role in sleep-wake regulation is unknown. To investigate whether functional variants in AQP4 modulate human sleep, nocturnal EEG recordings and cognitive performance were investigated in 123 healthy participants genotyped for a common eight-SNP AQP4-haplotype. We show that this AQP4-haplotype is associated with distinct modulations of NREM slow wave energy, strongest in early sleep and mirrored by changes in sleepiness and reaction times during extended wakefulness. The study provides the first human evidence for a link between AQP4, deep NREM sleep, and cognitive consequences of prolonged wakefulness.

中文翻译：

---

星形细胞水通道 AQP4 的单倍型与人类 NREM 睡眠中的慢波能量调节有关。

星形细胞水通道水通道蛋白 4 (AQP4) 促进了脑脊液 (CSF) 流过脑实质。稳态调节的脑电图 (EEG) 慢波是深度非快速眼动 (NREM) 睡眠的标志，并且与脑实质脑脊液流量和脑清除率的调节有关。人类 AQP4 基因含有几个与 AQP4 表达、脑水稳态和神经退行性疾病相关的单核苷酸多态性 (SNP)。迄今为止，它们在睡眠-觉醒调节中的作用尚不清楚。为了研究 AQP4 中的功能变异是否调节人类睡眠，研究了 123 名健康参与者的夜间脑电图记录和认知表现，这些参与者被基因分型为常见的八 SNP AQP4 单倍型。我们表明，这种 AQP4 单倍型与 NREM 慢波能量的不同调制有关，在早期睡眠中最强，并且反映在长时间清醒期间嗜睡和反应时间的变化。该研究为 AQP4、深度 NREM 睡眠和长时间清醒的认知后果之间的联系提供了第一个人类证据。