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However, how the brains of these subterranean mammals handle acute in vivo hypoxia is poorly understood. This study is the first to examine the molecular response to low oxygen in six different species of hypoxia-tolerant mole-rats from sub-Saharan Africa. Protein carbonylation, a known marker of DNA damage (hydroxy-2\u2019-deoxyguanosine), and antioxidant capacity did not change following hypoxia but HIF-1 protein levels increased significantly in the brains of two species. Nearly 30 miRNAs known to play roles in hypoxia-tolerance were differentially regulated in a species-specific manner. The miRNAs exhibiting the strongest response to low oxygen stress inhibit apoptosis and regulate neuroinflammation, likely providing neuroprotection. A principal component analysis using a subset of the molecular targets assessed herein revealed differences between control and hypoxic groups for two solitary species (Georychus capensis and Bathyergus suillus), which are ecologically adapted to a normoxic environment, suggesting a heightened sensitivity to hypoxia relative to species that may experience hypoxia more regularly in nature. By contrast, all molecular data were included in the PCA to detect a difference between control and hypoxic populations of eusocial Heterocephalus glaber, indicating they may require many lower-fold changes in signaling pathways to adapt to low oxygen settings. Finally, none of the Cryptomys hottentotus subspecies showed a statistical difference between control and hypoxic groups, presumably due to hypoxia-tolerance derived from environmental pressures associated with a subterranean and social lifestyle.<\/jats:p>","DOI":"10.1242\/jeb.215905","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T15:08:37Z","timestamp":1589209717000},"source":"Crossref","is-referenced-by-count":24,"title":["The brains of six African mole-rat species show divergent responses to hypoxia"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-3155","authenticated-orcid":false,"given":"Samantha M.","family":"Logan","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-1853","authenticated-orcid":false,"given":"Kama E.","family":"Szereszewski","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-2947","authenticated-orcid":false,"given":"Nigel C.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Mammal Research Institute and Department of Zoology & Entomology, University of Pretoria, Hatfield, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4592-558X","authenticated-orcid":false,"given":"Daniel W.","family":"Hart","sequence":"additional","affiliation":[{"name":"Mammal Research Institute and Department of Zoology & Entomology, University of Pretoria, Hatfield, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"van Jaarsveld","sequence":"additional","affiliation":[{"name":"Mammal Research Institute and Department of Zoology & Entomology, University of Pretoria, Hatfield, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-9555","authenticated-orcid":false,"given":"Matthew E.","family":"Pamenter","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Ottawa, Ottawa, ON, Canada"},{"name":"uOttawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7363-1853","authenticated-orcid":false,"given":"Kenneth B.","family":"Storey","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042623225890700_JEB215905C1","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.mad.2005.06.009","article-title":"Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked mole-rat","volume":"126","author":"Andziak","year":"2005","journal-title":"Mech. 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