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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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult AQP4 null mice and wild\u2010type (WT) mice were given 7\u00a0days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of \u03b2\u2010amyloid 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\u2010SD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that AQP4\u2010mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep\u2010related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13194","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T10:10:33Z","timestamp":1564567833000},"page":"228-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep 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