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

Rui Zhang, Yun Liu, Yan Chen, Qian Li, Charles Marshall, Ting Wu, Gang Hu, Ming Xiao

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Aims: 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). Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)228-239
Number of pages12
JournalCNS Neuroscience and Therapeutics
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Publisher Copyright:
© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Keywords

  • aquaporin-4
  • behavioral test
  • glymphatic system
  • hippocampus
  • sleep disruption

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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