{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:12:45Z","timestamp":1784041965413,"version":"3.55.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hypoxia is an environmental risk factor for many disorders throughout life. Perinatal hypoxia contributes to autism spectrum disorder (ASD), while hypoxic conditions in the elderly facilitate memory deficits. However, the effects of hypoxia on adolescence remains elusive. CNTNAP2 is a critical molecule in ASD pathogenesis with undefined mechanisms. We investigate hypoxia\u2019s impact on adolescence and the underlying mechanism related to CNTNAP2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three-chamber social approach test, Y maze, Morris Water Maze and Open Field Test were applied to evaluate behavioral alterations. Immunoblotting, 5\u2032- RACE and dual-luciferase reporter assay were performed to examine CNTNAP2 protein expression, transcription start site (TSS) of human CNTNAP2 gene and CNTNAP2 promoter activity, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intermittent hypoxia treatment improved social behaviors and working memory in adolescent mice. CNTNAP2 was increased in the brains of hypoxia-treated mice. The sequencing results identified the TSS at 518 bp upstream of the translation start site ATG. Hypoxia upregulated CNTNAP2 by interacting with functional hypoxia response elements in CNTNAP2 promoter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intermittent hypoxia enhanced sociability and working memory associated with CNTNAP2 upregulation. Our study provides novel insights into intermittent hypoxia\u2019s impact on development and the interaction between genetic and environmental risk factors in ASD pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2023.1155047","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T05:27:21Z","timestamp":1680758841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Qing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiye","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengen","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18120","DOI":"10.1073\/pnas.1216398109","article-title":"Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.","volume":"109","author":"Anderson","year":"2012","journal-title":"Proc. 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