1. Sleep is bi-directionally modified by amyloid beta oligomers.
- Author
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Özcan GG, Lim S, Leighton P, Allison WT, and Rihel J
- Subjects
- Alzheimer Disease complications, Animals, Membrane Proteins metabolism, Peptide Fragments metabolism, Prion Proteins physiology, Receptors, Adrenergic, beta-2 metabolism, Receptors, Progesterone metabolism, Signal Transduction genetics, Sleep Wake Disorders, Zebrafish genetics, Zebrafish Proteins metabolism, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Membrane Proteins genetics, Receptors, Adrenergic, beta-2 genetics, Receptors, Progesterone genetics, Sleep genetics, Zebrafish physiology, Zebrafish Proteins genetics
- 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., Competing Interests: GÖ, SL, PL, WA, JR No competing interests declared, (© 2020, Özcan et al.)
- Published
- 2020
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