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


Ulv Larsen, Sara Marie; Landolt, Hans-Peter; Berger, Wolfgang; Nedergaard, Maiken; Knudsen, Gitte Moos; Holst, Sebastian Camillo (2020). Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep. PLoS Biology, 18(5):e3000623.

Abstract

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.

Abstract

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Neuroscience
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > General Immunology and Microbiology
Life Sciences > General Agricultural and Biological Sciences
Uncontrolled Keywords:General Biochemistry, Genetics and Molecular Biology, General Immunology and Microbiology, General Neuroscience, General Agricultural and Biological Sciences
Language:English
Date:5 May 2020
Deposited On:29 Jun 2020 11:11
Last Modified:01 Aug 2020 18:50
Publisher:Public Library of Science (PLoS)
ISSN:1544-9173
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pbio.3000623
PubMed ID:32369477
Project Information:
  • : FunderH2020
  • : Grant ID798131
  • : Project TitleHuman Glymphatics - Effects of sleep deprivation and adrenergic inhibition on glymphatic flow in humans
  • : FunderSNSF
  • : Grant ID320030_135414
  • : Project TitleGlutamatergic mechanisms in sleep-wake homeostasis in health and disease - molecular brain imaging and pharmacogenetics
  • : FunderSNSF
  • : Grant ID320030_163439
  • : Project TitleGlutamatergic mechanisms in sleep-wake homeostasis - molecular brain imaging and pharmacogenetics

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