{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:21:19Z","timestamp":1788970879402,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of\u00a0histone acetyltransferases\u00a0and histone deacetylases (HDACs)\u00a0gene\u00a0expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3\u00a0and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat's hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2\u2009g\/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia\u2010exposed rats. Moreover, histone acetylation increased at the promoter regions of brain\u2010derived neurotrophic factor\u00a0(BDNF);\u00a0thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP\u2010response element binding protein (CREB) phosphorylation by stimulation of PI3K\/GSK3\u03b2\/CREB axis, which counteracts hypobaric hypoxia\u2010induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition.<\/jats:p>","DOI":"10.1002\/jcp.30337","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T05:20:52Z","timestamp":1617168052000},"page":"6754-6771","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["HDAC inhibition prevents hypobaric hypoxia\u2010induced spatial memory impairment through\u00a0P\u03993K\/GSK3\u03b2\/CREB pathway"],"prefix":"10.1002","volume":"236","author":[{"given":"Rahul","family":"Kumar","sequence":"first","affiliation":[{"name":"Neurobiology Division Defence Institute of Physiology and Allied Science (DIPAS), DRDO  Timarpur New Delhi 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