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Chronic Sleep Restriction Induces Aβ Accumulation by Disrupting the Balance of Aβ Production and Clearance in Rats

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Abstract

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aβ accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aβ42 deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of β-site APP-cleaving enzyme 1 (BACE1) and sAPPβ and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aβ42 level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aβ42 levels. In addition, CSR-21d rats had decreased plasma Aβ42 levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aβ accumulation in WT rats. The underlying mechanisms may be related to increased Aβ production via upregulation of the BACE1 pathway and disrupted Aβ clearance affecting brain and peripheral Aβ transport.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China to Qiumin Qu (No. 81771168).

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  1. Beiyu Zhao and Peng Liu contributed equally.

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, 710061, Xi’an, China

    Beiyu Zhao, Peng Liu, Meng Wei, Yanbo Li, Jie Liu, Louyan Ma, Suhang Shang, Yu Jiang, Kang Huo, Jin Wang & Qiumin Qu

  2. Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an, China

    Peng Liu

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  1. Beiyu Zhao
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Zhao, B., Liu, P., Wei, M. et al. Chronic Sleep Restriction Induces Aβ Accumulation by Disrupting the Balance of Aβ Production and Clearance in Rats. Neurochem Res 44, 859–873 (2019). https://doi.org/10.1007/s11064-019-02719-2

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