Cargando…

Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in h...

Descripción completa

Detalles Bibliográficos
Autores principales: Roh, Jee Hoon, Jiang, Hong, Finn, Mary Beth, Stewart, Floy R., Mahan, Thomas E., Cirrito, John R., Heda, Ashish, Snider, B. Joy, Li, Mingjie, Yanagisawa, Masashi, de Lecea, Luis, Holtzman, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267230/
https://www.ncbi.nlm.nih.gov/pubmed/25422493
http://dx.doi.org/10.1084/jem.20141788
_version_ 1782349126164283392
author Roh, Jee Hoon
Jiang, Hong
Finn, Mary Beth
Stewart, Floy R.
Mahan, Thomas E.
Cirrito, John R.
Heda, Ashish
Snider, B. Joy
Li, Mingjie
Yanagisawa, Masashi
de Lecea, Luis
Holtzman, David M.
author_facet Roh, Jee Hoon
Jiang, Hong
Finn, Mary Beth
Stewart, Floy R.
Mahan, Thomas E.
Cirrito, John R.
Heda, Ashish
Snider, B. Joy
Li, Mingjie
Yanagisawa, Masashi
de Lecea, Luis
Holtzman, David M.
author_sort Roh, Jee Hoon
collection PubMed
description Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain.
format Online
Article
Text
id pubmed-4267230
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-42672302015-06-15 Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease Roh, Jee Hoon Jiang, Hong Finn, Mary Beth Stewart, Floy R. Mahan, Thomas E. Cirrito, John R. Heda, Ashish Snider, B. Joy Li, Mingjie Yanagisawa, Masashi de Lecea, Luis Holtzman, David M. J Exp Med Brief Definitive Report Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain. The Rockefeller University Press 2014-12-15 /pmc/articles/PMC4267230/ /pubmed/25422493 http://dx.doi.org/10.1084/jem.20141788 Text en © 2014 Roh et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Roh, Jee Hoon
Jiang, Hong
Finn, Mary Beth
Stewart, Floy R.
Mahan, Thomas E.
Cirrito, John R.
Heda, Ashish
Snider, B. Joy
Li, Mingjie
Yanagisawa, Masashi
de Lecea, Luis
Holtzman, David M.
Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title_full Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title_fullStr Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title_full_unstemmed Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title_short Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
title_sort potential role of orexin and sleep modulation in the pathogenesis of alzheimer’s disease
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267230/
https://www.ncbi.nlm.nih.gov/pubmed/25422493
http://dx.doi.org/10.1084/jem.20141788
work_keys_str_mv AT rohjeehoon potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT jianghong potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT finnmarybeth potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT stewartfloyr potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT mahanthomase potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT cirritojohnr potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT hedaashish potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT sniderbjoy potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT limingjie potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT yanagisawamasashi potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT delecealuis potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease
AT holtzmandavidm potentialroleoforexinandsleepmodulationinthepathogenesisofalzheimersdisease