{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:16:02Z","timestamp":1793740562850,"version":"4.6.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/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":["2024ZD0529204"],"award-info":[{"award-number":["2024ZD0529204"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Obstructive Sleep Apnea (OSA) is a common sleep-disordered breathing condition characterized by recurrent upper airway collapse, chronic intermittent hypoxia (CIH), and sleep fragmentation. Beyond daytime dysfunction, OSA is strongly associated with cardiovascular and neuropsychiatric comorbidities, particularly hypertension and depression. The paraventricular nucleus of the hypothalamus (PVN), a central hub for autonomic regulation and stress integration, plays a pivotal role in mediating these outcomes. This review synthesizes recent evidence on the synergistic interplay between CIH and chronic stress within the PVN. We highlight three core mechanisms\u2014neuronal plasticity, neuroinflammation and oxidative stress, and epigenetic reprogramming\u2014that collectively drive sustained sympathetic overactivation and hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysregulation. These central alterations form the neurobiological basis of OSA-related hypertension and contribute to shared pathways with mood disorders, including oxidative stress and ferroptosis. Finally, we summarize emerging diagnostic and therapeutic advances, such as non-invasive biomarkers, phenotype-specific pharmacotherapies, and precision neuromodulation approaches. Future directions include the development of composite animal models, targeted epigenetic interventions, and circuit-specific modulation strategies. Together, these insights provide a framework for mechanism-based and stratified management of OSA and its comorbidities.<\/jats:p>","DOI":"10.3389\/fneur.2026.1720898","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:44:20Z","timestamp":1779943460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PVN mechanisms in OSA comorbidities: from intermittent hypoxia\u2013stress to therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Haiying","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Information and Data Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.3390\/ijms20122937","article-title":"Epigenetics: a potential mechanism involved in the pathogenesis of various adverse consequences of obstructive sleep apnea","volume":"20","author":"Chen","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"10701","DOI":"10.3390\/ijms221910701","article-title":"Chronic and cycling hypoxia: drivers of cancer chronic inflammation through HIF-1 and NF-kappaB activation: a 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