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.
Friday, May 8, 2026
Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice
Novelli EM, Lenhart SC, Foley LM, Sekar N, Mondal P, Wang H, Hitchens TK, Ghosh S, Chan SY, Hu X, Hazra R. Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice. PNAS Nexus. 2026 Apr 8;5(4):pgag106. doi: 10.1093/pnasnexus/pgag106. PMID: 42037666; PMCID: PMC13108596.
