Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep
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Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep. / Larsen, Sara Marie Ulv; Landolt, Hans Peter; Berger, Wolfgang; Nedergaard, Maiken; Knudsen, Gitte Moos; Holst, Sebastian Camillo.
In: PLOS Biology, Vol. 18, No. 5, e3000623, 05.2020.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep
AU - Larsen, Sara Marie Ulv
AU - Landolt, Hans Peter
AU - Berger, Wolfgang
AU - Nedergaard, Maiken
AU - Knudsen, Gitte Moos
AU - Holst, Sebastian Camillo
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pbio.3000623
DO - 10.1371/journal.pbio.3000623
M3 - Journal article
C2 - 32369477
AN - SCOPUS:85084277504
VL - 18
JO - PLoS Biology
JF - PLoS Biology
SN - 1544-9173
IS - 5
M1 - e3000623
ER -
ID: 246871339