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Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice.
J Alzheimers Dis. 2016; 50(3):669-85.JA

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+Show Affiliations

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.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.The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, P.R. China.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26757041

Citation

Qiu, Hongyan, et al. "Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice." Journal of Alzheimer's Disease : JAD, vol. 50, no. 3, 2016, pp. 669-85.
Qiu H, Zhong R, Liu H, et al. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice. J Alzheimers Dis. 2016;50(3):669-85.
Qiu, H., Zhong, R., Liu, H., Zhang, F., Li, S., & Le, W. (2016). Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice. Journal of Alzheimer's Disease : JAD, 50(3), 669-85. https://doi.org/10.3233/JAD-150774
Qiu H, et al. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice. J Alzheimers Dis. 2016;50(3):669-85. PubMed PMID: 26757041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice. AU - Qiu,Hongyan, AU - Zhong,Rujia, AU - Liu,Hui, AU - Zhang,Feng, AU - Li,Song, AU - Le,Weidong, PY - 2016/1/13/entrez PY - 2016/1/13/pubmed PY - 2016/11/1/medline KW - Alzheimer’s disease KW - amyloid-β KW - apoptosis KW - chronic sleep deprivation KW - mitochondria KW - phosphorylated tau protein KW - senile plaques SP - 669 EP - 85 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 50 IS - 3 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26757041/Chronic_Sleep_Deprivation_Exacerbates_Learning_Memory_Disability_and_Alzheimer's_Disease_Like_Pathologies_in_AβPP_swe_/PS1_ΔE9__Mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-150774 DB - PRIME DP - Unbound Medicine ER -