Fig. 5
From: Microglial ferroptotic stress causes non-cell autonomous neuronal death
ALS model mice recapitulate features of ferroptosis and neurotoxic glia evident in human ALS-affected spinal cord. a-d Markers associated with iron are perturbed in spinal cord of transgenic SOD1G37R ALS model mice (ALS-Tg) compared to non-transgenic littermates (Control), including elevated iron, diminished ferroxidase activity and altered expression of iron handling genes. e-h Spinal cord tissue from transgenic SOD1G37R ALS model mice display features of ferroptosis, including elevated lipid peroxidation, diminished GPX4 protein level, and altered transcripts for ferroptosis related genes. i, j Relative expression changes for genes associated with neurotoxic glial activation in spinal cord of SOD1G37R and control mice. Violin plots in j represent overall transcript signature for features indicated, derived from heatmap data shown in i, including genes associated with neurotoxicity in vitro (Neurotoxic; shown in Supplementary Fig. 7). k Representative immunofluorescence for microglial marker IBA1 (magenta), ferroptosis-related protein ALOX5 (green) and nuclear marker DAPI (blue) in spinal cord ventral horn of SOD1G37R and control mice. l Microglial ALOX5 quantitated from k. m Representative immunofluorescence for IBA1 (magenta), ferroptosis-related protein LPCAT3 (green) and DAPI (blue) in spinal cord ventral horn of SOD1G37R and control mice. n Microglial LPCAT3 quantitated from m. Data in e and f are expressed relative to controls. P values show significant differences where indicated. Data points (a, b, d-f, h, j, l, n) represent individual SOD1G37R or control animals. Error margins in a, b, e, f, l, n are S.E.M. Values in transcript heatmaps (c, g, i) represent z-scores for individual SOD1G37R or control animals, and crosses represent excluded samples. Violin plots in d, h, j represent overall transcript signature derived from heatmap data shown in c, g, i, respectively, where solid lines represent median, dotted lines represent 25th/75th percentiles, truncated at min-max values. Outline of IBA1-positive microglia are overlaid with ALOX5 and LPCAT3 in k and m, respectively. Scale bar (k, m) = 20 µm