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To understand the mechanisms that facilitate neuronal preservation during hypoxia, we investigated the proteins regulating hypoxia tolerance in NMR hippocampal neurons. Caveolin\u20101 (Cav\u20101), a transmembrane scaffolding protein, confers prosurvival signalling in the central nervous system. The present study aimed to investigate the role of Cav\u20101 in hypoxia\u2010induced neuronal injury. Western blotting analysis and immunocytochemistry showed that Cav\u20101 expression was significantly upregulated in NMR hippocampal neurons under 8% O<jats:sub>2<\/jats:sub> conditions for 8\u2009h. Cav\u20101 alleviates apoptotic neuronal death from hypoxia. Downregulation of Cav\u20101 by lentiviral vectors suggested damage to NMR hippocampal neurons under hypoxic conditions in vitro and in vivo. Overexpression of Cav\u20101 by LV\u2010Cav\u20101 enhanced hypoxic tolerance of NMR hippocampal neurons in vitro and in vivo. Mechanistically, the levels of hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1) are also increased under hypoxic conditions. After inhibiting the binding of HIF\u20101\u03b1 to hypoxia response elements in the DNA by echinomycin, Cav\u20101 levels were downregulated significantly. Furthermore, chromatin immunoprecipitation assays showed the direct role of HIF1\u03b1 in regulating the expression levels of Cav\u20101 in NMR hippocampal neurons under hypoxic conditions. These findings suggest that Cav\u20101 plays a critical role in modulating the apoptosis of NMR hippocampal neurons and warrant further studies targeting Cav\u20101 to treat hypoxia\u2010associated brain diseases.<\/jats:p>","DOI":"10.1002\/cbin.11890","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T17:29:57Z","timestamp":1662139797000},"page":"2060-2074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Caveolin\u20101 suppresses hippocampal neuron apoptosis via the regulation of HIF1\u03b1 in hypoxia in naked mole\u2010rats"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-9341","authenticated-orcid":false,"given":"Wenjing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Sciences, School of Basic Medicine Naval Medical University Shanghai 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