{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:28:17Z","timestamp":1787160497477,"version":"build-2736575974"},"reference-count":63,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Key Research Project","award":["2023C03079"],"award-info":[{"award-number":["2023C03079"]}]},{"name":"Start-up Fund","award":["OJQDSP2022007"],"award-info":[{"award-number":["OJQDSP2022007"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFE0210100"],"award-info":[{"award-number":["2022YFE0210100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Initiative STI2030-Major Projects","award":["2021ZD0203400"],"award-info":[{"award-number":["2021ZD0203400"]}]},{"name":"Ningbo Top Medical and Health Research Program","award":["2022020304"],"award-info":[{"award-number":["2022020304"]}]},{"DOI":"10.13039\/501100018553","name":"Science and Technology Plan Project of Wenzhou, China","doi-asserted-by":"publisher","award":["Y2023307"],"award-info":[{"award-number":["Y2023307"]}],"id":[{"id":"10.13039\/501100018553","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LY24H010004"],"award-info":[{"award-number":["LY24H010004"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571695"],"award-info":[{"award-number":["82571695"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870073"],"award-info":[{"award-number":["81870073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic intermittent hypoxia (CIH), a defining feature of obstructive sleep apnea, is strongly associated with cognitive impairment and increased risk of neurodegenerative disease, yet the underlying mechanisms linking hypoxic stress to disrupted brain homeostasis remain poorly defined. Impaired glymphatic clearance has been reported in patients with obstructive sleep apnea, but whether and how intermittent hypoxia directly alters glymphatic function is unknown. Here, we investigated the effects of acute and chronic intermittent hypoxia on cerebrospinal fluid\u2013interstitial fluid exchange in male mice and examined the molecular mechanisms governing these effects. Using tracer-based influx and efflux assays, in vivo two-photon imaging, behavioral testing, and genetic and pharmacological manipulation, we show that intermittent hypoxia exerts a duration-dependent, biphasic effect on glymphatic function. Acute exposure transiently enhanced glymphatic influx and efflux, whereas prolonged CIH progressively impaired glymphatic transport, disrupted perivascular aquaporin-4 (AQP4) polarization, reduced vascular pulsatility, and impaired spatial working memory. CIH was associated with reduced extracellular adenosine levels, suppression of cerebral energy metabolism, and altered expression of equilibrative nucleoside transporters (ENTs). Genetic ablation of AQP4 abolished CIH-induced glymphatic impairment, confirming its essential role in hypoxia-induced glymphatic dysfunction. Importantly, pharmacological inhibition or genetic deletion of ENT1 and deletion of ENT2 restored adenosine availability, normalized AQP4 polarization and vascular dynamics, and rescued glymphatic dysfunction and cognitive deficits under CIH. These findings identify ENT-dependent dysregulation of adenosine signaling as a key mechanism by which chronic intermittent hypoxia compromises glymphatic clearance, providing mechanistic insight into how sleep-disordered breathing disrupts brain waste removal and cognitive function.<\/jats:p>","DOI":"10.1093\/sleep\/zsag182","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:23:04Z","timestamp":1783336984000},"source":"Crossref","is-referenced-by-count":1,"title":["Chronic intermittent hypoxia impairs glymphatic function in male mice through equilibrative nucleoside transporter\u2013dependent adenosine dysregulation"],"prefix":"10.1093","author":[{"given":"Chenlei","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Sun","sequence":"additional","affiliation":[{"name":"The Eye and Brain Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Eye and Brain Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Jia","sequence":"additional","affiliation":[{"name":"The Eye and Brain Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Jin","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[{"name":"The Eye and Brain Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Neuroscience Medical Center, Ningbo Medical Center Lihuili Hospital, Ningbo University , Ningbo ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Eye and Brain Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]},{"name":"Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-3495","authenticated-orcid":false,"given":"Xuzhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University , Ningbo ,","place":["China"]},{"name":"Department of Psychosomatic Medicine, the First Affiliated Hospital of Ningbo University, Zhejiang Regional Medical Center , Ningbo, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"issue":"8","key":"2026080814064681300_ref1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S2213-2600(19)30198-5","article-title":"Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis","volume":"7","author":"Benjafield","year":"2019","journal-title":"Lancet Respir 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