{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:22:17Z","timestamp":1788387737878,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R56NS109908"],"award-info":[{"award-number":["R56NS109908"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1RF1AG059621"],"award-info":[{"award-number":["1RF1AG059621"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Aging","award":["R56NS109908"],"award-info":[{"award-number":["R56NS109908"]}]},{"name":"National Institute of Aging","award":["1RF1AG059621"],"award-info":[{"award-number":["1RF1AG059621"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-\u03b1) chains and two Hb-beta (Hb-\u03b2) chains. A number of studies have also shown that Hb-\u03b1 is also expressed in neurons in both the rodent and human brain. In the current study, we examined for age-related regulation of neuronal Hb-\u03b1 and hypoxia in the hippocampus and cerebral cortex of intact male and female mice. In addition, to confirm the role and functions of neuronal Hb-\u03b1, we also utilized lentivirus CRISPR interference-based Hb-\u03b1 knockdown (Hb-\u03b1 CRISPRi KD) in the non-ischemic and ischemic mouse hippocampus and examined the effect on neuronal oxygenation, as well as induction of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and its downstream pro-apoptotic factors, PUMA and NOXA, and on neuronal survival and neurodegeneration. The results of the study revealed an age-related decrease in neuronal Hb-\u03b1 levels and correlated increase in hypoxia in the hippocampus and cortex of intact male and female mice. Sex differences were observed with males having higher neuronal Hb-\u03b1 levels than females in all brain regions at all ages. In vivo Hb-\u03b1 CRISPRi KD in the mouse hippocampus resulted in increased hypoxia and elevated levels of HIF-1\u03b1, PUMA and NOXA in the non-ischemic and ischemic mouse hippocampus, effects that were correlated with a significant decrease in neuronal survival and increased neurodegeneration. As a whole, these findings indicate that neuronal Hb-\u03b1 decreases with age in mice and has an important role in regulating neuronal oxygenation and neuroprotection.<\/jats:p>","DOI":"10.3390\/ijms23105360","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T10:19:46Z","timestamp":1652264386000},"page":"5360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus"],"prefix":"10.3390","volume":"23","author":[{"given":"Yujiao","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday P.","family":"Pratap","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangadhara R.","family":"Sareddy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan M.","family":"Dhandapani","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Capuano","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Arvanitakis","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna K.","family":"Vadlamudi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-8859","authenticated-orcid":false,"given":"Darrell W.","family":"Brann","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.bcmd.2017.10.006","article-title":"Structure and function of haemoglobins","volume":"70","author":"Gell","year":"2018","journal-title":"Blood Cells Mol. 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