PUBLICATION

Sleep is bi-directionally modified by amyloid beta oligomers

Authors
Özcan, G.G., Lim, S., Leighton, P., Allison, W.T., Rihel, J.
ID
ZDB-PUB-200715-18
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Allison, Ted, Leighton, Patricia, Rihel, Jason
Keywords
alzheimer's disease, amyloid beta, behavior, neuroscience, prion protein, sleep, zebrafish
MeSH Terms
  • Alzheimer Disease/complications
  • Alzheimer Disease/metabolism*
  • Amyloid beta-Peptides/metabolism*
  • Animals
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • Peptide Fragments/metabolism
  • Prion Proteins/physiology
  • Receptors, Adrenergic, beta-2/genetics*
  • Receptors, Adrenergic, beta-2/metabolism
  • Receptors, Progesterone/genetics*
  • Receptors, Progesterone/metabolism
  • Signal Transduction/genetics
  • Sleep/genetics*
  • Sleep Wake Disorders
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
32660691 Full text @ Elife
Abstract
Disrupted sleep is a major feature of Alzheimer's disease (AD), often arising years before symptoms of cognitive decline. Prolonged wakefulness exacerbates the production of amyloid-beta (Aβ) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which Aβ affects sleep are unknown. We demonstrate in zebrafish that Aβ acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genetic disruptions revealed that short Aβ oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1), while longer Aβ forms induce sleep through a pharmacologically tractable Prion Protein (PrP) signaling cascade. Our data indicate that Aβ can trigger a bi-directional sleep/wake switch. Alterations to the brain's Aβ oligomeric milieu, such as during the progression of AD, may therefore disrupt sleep via changes in acute signaling events.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping