title: Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.
abstract: Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPP(swe)/PS1(ΔE9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qiu
authors.affiliation: The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, P.R. China.
authors.forename: Rujia
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.|The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D020287:In Situ Nick-End Labeling; D007859:Learning Disabilities / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D028361:Mitochondrial Diseases / Q000209:etiology / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics; D012193:Reversal Learning / Q000502:physiology; D012892:Sleep Deprivation / Q000150:complications*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016875:tau Proteins
keywords: Alzheimer’s disease; amyloid-β; apoptosis; chronic sleep deprivation; mitochondria; phosphorylated tau protein; senile plaques