학술논문
Late-in-life neurodegeneration after chronic sleep loss in young adult mice
ORIGINAL ARTICLE
ORIGINAL ARTICLE
Document Type
Academic Journal
Author
Source
SLEEP. August 2021, Vol. 44 Issue 8, p1o, 12 p.
Subject
Language
English
ISSN
0161-8105
Abstract
Introduction There are approximately 50 million individuals worldwide with dementia, most of whom have Alzheimer's disease (AD) [1], and as the population ages, the number of individuals with AD is [...]
Chronic short sleep (CSS) is prevalent in modern societies and has been proposed as a risk factor for Alzheimer's disease (AD). In support, short-term sleep loss acutely increases levels of amyloid [beta] (A[beta]) and tau in wild type (WT) mice and humans, and sleep disturbances predict cognitive decline in older adults. We have shown that CSS induces injury to and loss of locus coeruleus neurons (LCn), neurons with heightened susceptibility in AD. Yet whether CSS during young adulthood drives lasting A[beta] and/or tau changes and/or neural injury later in life in the absence of genetic risk for AD has not been established. Here, we examined the impact of CSS exposure in young adult WT mice on late-in-life A[beta] and tau changes and neural responses in two AD-vulnerable neuronal groups, LCn and hippocampal CA1 neurons. Twelve months following CSS exposure, CSS-exposed mice evidenced reductions in CA1 neuron counts and volume, spatial memory deficits, CA1 glial activation, and loss of LCn. [A[beta].sub.42] and hyperphosphorylated tau were increased in the CA1; however, amyloid plaques and tau tangles were not observed. Collectively the findings demonstrate that CSS exposure in the young adult mouse imparts late-in-life neurodegeneration and persistent derangements in amyloid and tau homeostasis. These findings occur in the absence of a genetic predisposition to neurodegeneration and demonstrate for the first time that CSS can induce lasting, significant neural injury consistent with some, but not all, features of late-onset AD. Key words: sleep deprivation; partial sleep restriction; noradrenergic; pyramidal neurons; stereology; microglial dysfunction
Chronic short sleep (CSS) is prevalent in modern societies and has been proposed as a risk factor for Alzheimer's disease (AD). In support, short-term sleep loss acutely increases levels of amyloid [beta] (A[beta]) and tau in wild type (WT) mice and humans, and sleep disturbances predict cognitive decline in older adults. We have shown that CSS induces injury to and loss of locus coeruleus neurons (LCn), neurons with heightened susceptibility in AD. Yet whether CSS during young adulthood drives lasting A[beta] and/or tau changes and/or neural injury later in life in the absence of genetic risk for AD has not been established. Here, we examined the impact of CSS exposure in young adult WT mice on late-in-life A[beta] and tau changes and neural responses in two AD-vulnerable neuronal groups, LCn and hippocampal CA1 neurons. Twelve months following CSS exposure, CSS-exposed mice evidenced reductions in CA1 neuron counts and volume, spatial memory deficits, CA1 glial activation, and loss of LCn. [A[beta].sub.42] and hyperphosphorylated tau were increased in the CA1; however, amyloid plaques and tau tangles were not observed. Collectively the findings demonstrate that CSS exposure in the young adult mouse imparts late-in-life neurodegeneration and persistent derangements in amyloid and tau homeostasis. These findings occur in the absence of a genetic predisposition to neurodegeneration and demonstrate for the first time that CSS can induce lasting, significant neural injury consistent with some, but not all, features of late-onset AD. Key words: sleep deprivation; partial sleep restriction; noradrenergic; pyramidal neurons; stereology; microglial dysfunction