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Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption.

Authors
  • Zhang, Rui1, 2
  • Liu, Yun1, 2
  • Chen, Yan2, 3
  • Li, Qian2, 3
  • Marshall, Charles4
  • Wu, Ting1, 2
  • Hu, Gang2
  • Xiao, Ming2, 3
  • 1 Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. , (China)
  • 2 Jiangsu Province, Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China. , (China)
  • 3 Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China. , (China)
  • 4 Department of Rehabilitation Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, KY, USA.
Type
Published Article
Journal
CNS Neuroscience & Therapeutics
Publisher
Wiley (Blackwell Publishing)
Publication Date
Feb 01, 2020
Volume
26
Issue
2
Pages
228–239
Identifiers
DOI: 10.1111/cns.13194
PMID: 31364823
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD). Adult AQP4 null mice and wild-type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses. Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of β-amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT-SD mice. These results demonstrate that AQP4-mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep-related disorders. © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

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