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
Citation
Özcan, G.G., Lim, S., Leighton, P., Allison, W.T., Rihel, J. (2020) Sleep is bi-directionally modified by amyloid beta oligomers. eLIFE. 9:.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping