{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:40:18Z","timestamp":1777628418769,"version":"3.51.4"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["1R21NS131634-01A1"],"award-info":[{"award-number":["1R21NS131634-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["R01DK124426"],"award-info":[{"award-number":["R01DK124426"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["R01DK132145"],"award-info":[{"award-number":["R01DK132145"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01 HL124021"],"award-info":[{"award-number":["R01 HL124021"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["HL122596"],"award-info":[{"award-number":["HL122596"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["HL151228"],"award-info":[{"award-number":["HL151228"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Individuals with sickle cell disease (SCD) suffer from a high burden of neurocognitive impairment. Cerebrovascular lesions, characterized by diffusion tensor imaging identified neuroaxonal damage, are associated with learning and memory deficits. The molecular and cellular intermediates driving microstructural neuroaxonal damage and cognitive impairment in SCD remain largely unexplored. Herein, we report that sickle cell mice (SS) have reduced expression of frataxin (FXN), a mitochondrial protein, in their astrocytes compared with normal control (AA) mice. A newly generated sickle bone marrow chimeric mouse with astrocyte-specific deletion of FXN (SSFXN-KO) showed worsening white-matter neuroaxonal damage compared with the normal mice lacking astrocytic FXN (AAFXN-KO) as well as with the SS mice with wild-type FXN expression (SSFXN-WT). The SSFXN-KO mice exhibited impaired cognitive function assessed by the functional novel object recognition (NOR) tests. Induction of FXN improved cognitive responses in the SS mice. Overall, our data demonstrate that astrocytic FXN plays a pivotal role in regulating neuroaxonal health and cognitive function in SCD.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgag106","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:27:10Z","timestamp":1775910430000},"source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8285","authenticated-orcid":false,"given":"Enrico M","family":"Novelli","sequence":"first","affiliation":[{"name":"Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute and Division of Classical Hematology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2595-9379","authenticated-orcid":false,"given":"Shane 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,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2608-6645","authenticated-orcid":false,"given":"Paritosh","family":"Mondal","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute and Division of Classical Hematology, Department of Medicine, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-2908","authenticated-orcid":false,"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T Kevin","family":"Hitchens","sequence":"additional","affiliation":[{"name":"Advanced Imaging Center, Department of Neurobiology, University of Pittsburgh , Pittsburgh, PA 15203 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