Fig. 5.
Neonatal anemia in Hif-2αIntKO pups leads to long-term cognitive defects. (A) Brain iron staining performed using enhanced Prussian blue stain in 2-wk-old and 8-wk-old pups born to Hif-2αF/F and Hif-2αIntKO mothers. The 8-wk-old pups were nursing from Hif-2αF/F and Hif-2αIntKO mothers until weaning at 21 d, following which the pups were placed on a regular chow diet. (B) Cognitive test performed using ANY-Maze in 8-wk-old pups born to Hif-2αF/F, Hif-2αIntKO, or iron dextran-injected Hif-2αIntKO mothers. (C) Immunostaining for phospho-CREB in the CA3 region of hippocampus. (D) qPCR analysis of nerve growth factor-1 (NGF-1), activity-regulated cytoskeleton-associated protein (Arc), c-FOS, and brain-derived neurotrophic factor (BDNF) in the hippocampus of 8-wk-old mice born to Hif-2αF/F, Hif-2αIntKO, or iron dextran-injected Hif-2αIntKO mothers. Expression was normalized to β-actin and each bar represents the mean value ± SEM #P < 0.05 vs. HIF-2αF/F; *P < 0.05 vs. HIF-2αIntKO; **P < 0.01 vs. HIF-2αIntKO. Seven to nine litters were assessed per genotype.