Fig. 5. Detoxification pathway differences between human and mouse astrocytes.

a, b Expression of ROS detoxification pathway genes catalase (a) and glucose-6-phosphate dehydrogenase (G6pd in human/G6pdx in mouse) (b) by acutely purified astrocytes and serum-free cultures of astrocytes determined by RNA-seq. N = 6 litters of mice and 18 human patients for acutely purified samples. N = 14 litters of mice and 9 human patients in vitro. Acutely purified: Catalase, p < 0.0001; G6PD, p < 0.0001, two-tailed Mann-Whitney test. Serum-free cultures: Catalase, p < 0.0001; G6PD, p < 0.0001. Two-tailed unpaired Welch’s t-test, unless otherwise indicated. Samples include children and adult patients as well as developing and adult mice. The ages of the patients and mice are listed in Supplementary Data 8. c Non-mitochondrial OCR measured in the presence of antimycin-A. N = 7 wells of cultured cells from each species generated from 4 litters of mice and 3 patients. p = 0.0126. Two-tailed unpaired Welch’s t-test. The p-values were calculated using average results from each litter of mice and each patient as independent observations. d, e Model of glucose metabolism and detoxification pathways in human and mouse astrocytes. The widths of the arrows represent the rate of the metabolic processes. Mouse astrocytes have higher rates of oxidative phosphorylation, which presumably produce more ROS than human astrocytes. The higher abundance of detoxification pathway genes and the higher peroxisomal activity in mouse compared to human may protect the cells against oxidative damage.