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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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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 |
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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 |
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