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In this study, we show that sublethal RH increased anxiety, impaired learning and memory (L\/M), and triggered downregulation of brain levels of glucose and several glucose metabolites in zebrafish, and that supplementation of glucose or glucosamine (GlcN) restored RH-induced L\/M impairment. Fear conditioning (FC)-induced brain activation of and PKA\/CREB signaling was abrogated by RH, and this effect was reversed by GlcN supplementation. RH was associated with decreased brain O-GlcNAcylation and an increased O-GlcNAcase (OGA) level. RH increased brain inflammation and p-Tau and amyloid \u03b2 accumulation, and these effects were suppressed by GlcN. Our observations collectively suggest that changes in O-GlcNAc flux during hypoxic exposure could be an important causal factor for neurodegeneration, and that supplementation of the HBP\/ O-GlcNAc flux may be a potential novel therapeutic or preventive target for addressing hypoxic brain damage.<\/jats:p>","DOI":"10.1177\/0271678x211027381","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T06:58:31Z","timestamp":1624690711000},"page":"3111-3126","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloid\u03b2\/\n                    <i>p<\/i>\n                    -Tau accumulation through reduced brain\n                    <i>O<\/i>\n                    -GlcNAcylation in zebrafish"],"prefix":"10.1177","volume":"41","author":[{"given":"Jiwon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Program in Biomedical Science and Engineering, College of Medicine, Inha University, Incheon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee","family":"Jung","sequence":"additional","affiliation":[{"name":"Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Program in Biomedical Science and Engineering, College of Medicine, Inha University, Incheon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Program in Biomedical Science and Engineering, College of 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