Sleep is bi-directionally modified by amyloid beta oligomers.
Elife
; 92020 07 14.
Article
en En
| MEDLINE
| ID: mdl-32660691
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 (Aß) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which Aß affects sleep are unknown. We demonstrate in zebrafish that Aß acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genetic disruptions revealed that short Aß oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1), while longer Aß forms induce sleep through a pharmacologically tractable Prion Protein (PrP) signaling cascade. Our data indicate that Aß can trigger a bi-directional sleep/wake switch. Alterations to the brain's Aß oligomeric milieu, such as during the progression of AD, may therefore disrupt sleep via changes in acute signaling events.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sueño
/
Pez Cebra
/
Receptores de Progesterona
/
Péptidos beta-Amiloides
/
Receptores Adrenérgicos beta 2
/
Proteínas de Pez Cebra
/
Enfermedad de Alzheimer
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Reino Unido