{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:14:55Z","timestamp":1791220495449,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1104300"],"award-info":[{"award-number":["2022YFA1104300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>High\u2010altitude cerebral edema (HACE) leads to cognitive decline, but the underlying cellular and molecular mechanisms remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established a mouse model of HACE under hypobaric hypoxia (simulating at an altitude of 6000\u2009m) and analyzed hippocampal changes using single\u2010cell RNA sequencing (scRNA\u2010seq) and spatial transcriptomics (ST) at 3\u2009days and 7\u2009days post\u2010exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypobaric hypoxia induced HACE and cognitive decline by altering the transcriptomic profiles and interactions of oligodendrocytes (MOL and MOL2) and neurons (ExN\u2010L6\u2010CT\u20102). Early upregulation of PI3K\/mTOR in oligodendrocytes mitigated Rps29\u2010bax\u2010mediated ribosomal stress and oxidative phosphorylation, promoting survival and myelin repair. Prolonged hypoxia suppressed PI3K\/mTOR, triggering apoptosis\/autophagy via oxidative phosphorylation and ribosomal stress. Enhanced Tnfrsf21\u2010App interactions between MOL2 and ExN\u2010L6\u2010CT\u20102 exacerbated neuroinflammation and cognitive decline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study reveals that HACE\u2010induced cognitive impairment is closely associated with dysregulated ribosomal stress and oxidative phosphorylation and impaired neuroactive ligand\u2010receptor interactions. Furthermore, we identify PI3K\/mTOR dynamics, Rps29\u2010bax\u2010axis, and Tnfrsf21\u2010App as novel regulators, offering potential therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70485","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T05:46:29Z","timestamp":1750657589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Single\u2010Cell <scp>RNA<\/scp> Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte\u2013Neuron Interaction in Cognitive Decline After High\u2010Altitude Cerebral Edema"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8798-0930","authenticated-orcid":false,"given":"Wenying","family":"Lv","sequence":"first","affiliation":[{"name":"The Second School of Clinical Medicine Southern Medical University  Guangzhou China"},{"name":"Department of Hyperbaric Oxygen 6th Medical Center of 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