Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep

by Sara Marie Ulv Larsen, Hans-Peter Landolt, Wolfgang Berger, Maiken Nedergaard, Gitte Moos Knudsen, Sebastian Camillo Holst 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 humanAQP4 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 inAQP4 modulate human sleep, nocturnal EEG recordings and cognitive performance were investigated in 123 healthy participants genotyped for a common eight-SNPAQP4-haplotype. We show that thisAQP4-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.
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research