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

Autor: Ulv Larsen SM; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Landolt HP; Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.; Sleep & Health Zurich, University Center of Competence, Zurich, Switzerland., Berger W; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland.; Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland., Nedergaard M; Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark., Knudsen GM; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Holst SC; Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Sleep & Health Zurich, University Center of Competence, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2020 May 05; Vol. 18 (5), pp. e3000623. Date of Electronic Publication: 2020 May 05 (Print Publication: 2020).
DOI: 10.1371/journal.pbio.3000623
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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