{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:43Z","timestamp":1785421783054,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400974"],"award-info":[{"award-number":["32400974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32400974"],"award-info":[{"award-number":["32400974"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Hypoxia signaling and the circadian clock exhibit extensive molecular crosstalk, but how endogenous circadian timing influences behavioral responses during high-altitude exposure remains incompletely understood. Methods: Male C57BL\/6J mice were exposed to hypobaric hypoxia equivalent to an altitude of 6000 m. Wheel-running activity was continuously monitored under 12 h light\/12 h dark (LD) cycle and constant-dark conditions to evaluate locomotor activity, rhythm amplitude, circadian phase, and free-running period. After 48 h of exposure, whole-hypothalamus samples were collected across the circadian cycle for time-series RNA sequencing, rhythmicity and pathway-enrichment analyses, and qPCR validation. In a separate experiment, hypoxia was initiated at ZT2 or ZT14 to assess circadian-phase-dependent behavioral responses. Results: High-altitude exposure acutely reduced locomotor activity and rhythm amplitude and subsequently delayed behavioral circadian phase under a LD cycle, whereas the free-running period under constant darkness remained unchanged. Transcriptomic analysis revealed extensive remodeling of rhythmic gene expression in the whole hypothalamus, involving multiple signaling and metabolic pathways. Relaxin-related signaling emerged as a candidate pathway associated with hypoxia-induced temporal transcriptional remodeling, and selected core clock genes and relaxin pathway-associated genes showed altered temporal expression profiles. Furthermore, exposure initiated at ZT14 produced greater locomotor suppression than exposure initiated at ZT2. Conclusions: High-altitude exposure disrupts behavioral circadian organization and remodels hypothalamic rhythmic transcription. These findings suggest that endogenous circadian timing modulates behavioral sensitivity to hypoxic stress.<\/jats:p>","DOI":"10.3390\/cells15151335","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plateau Hypoxia Influences Mouse Circadian Behavior by Remodeling the Hypothalamic Transcriptional Landscape"],"prefix":"10.3390","volume":"15","author":[{"given":"Chang","family":"Lu","sequence":"first","affiliation":[{"name":"Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-1063","authenticated-orcid":false,"given":"Zeqi","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"},{"name":"College of Biological Sciences, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengpu","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohong","family":"Nie","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Yin","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-2523","authenticated-orcid":false,"given":"Bo","family":"Cui","sequence":"additional","affiliation":[{"name":"Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Fu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev-physiol-021909-135821","article-title":"The mammalian circadian timing system: Organization and coordination of central and peripheral clocks","volume":"72","author":"Dibner","year":"2010","journal-title":"Annu. 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