Fig. 2: AR mRNA expression in IBA1+ microglia/macrophages is up-regulated in the human female MS brain.

Post-mortem white matter samples from MS and non-neurological control donors were used to detect AR mRNA expression in fluorescently labeled IBA1⁺ microglia/macrophages. a Representative images showing AR mRNA expression (red) within Iba1⁺ microglia/macrophages (cyan) in white matter from a female control donor and in active white matter demyelinated lesions from a female and male MS donor. Sections were counterstained with DAPI (blue). Scale bar 50 μm. Magnified regions in inserts show AR⁺ (white arrowheads) and AR^– (yellow arrowheads) microglia/macrophages. Scale bar 20 μm. b Quantification of RNAscope experiment shows a significantly greater proportion of Iba1⁺ cells expressing AR mRNA in MS samples compared to controls (F _{1, 18} = 8.778, p = 0.00821; post-hoc pairwise comparison: t = 2.963, p = 0.0083; control: median 34.70 (CI 30.00, 37.47), 25% percentile 32.50, 75% percentile 35.98, minimum 25.00, maximum 40.10; MS: median 46.60 (CI 31.92, 52.00), 25% percentile 33.33, 75% percentile 51.43, minimum 25.77, maximum 66.00), with a significant effect of sex, as significantly more Iba1⁺ cells express AR in females compared to males (linear mixed-effect model: F _{1, 18} = 10.411, p = 0.00459; post-hoc pairwise comparison: t = 3.231, p = 0.0046). c Within MS donors, female samples show a significantly greater proportion of AR⁺Iba1⁺ cells compared to males (F _{1, 8} = 28.579, p = 0.000494). No significant differences were detected among different lesion types (F _{3, 97} = 2.027, p = 0.1151; WM: median 34.70 (CI 30.00, 37.47), 25% percentile 32.50, 75% percentile 35.98, minimum 25.00, maximum 40.10; CIL: median 45.41 (CI 22.94, 56.00), 25% percentile 32.89, 75% percentile 52.28, minimum 22.94, maximum 56.00; AL: median 46.60 (CI 25.00, 72.03), 25% percentile 31.54, 75% percentile 59.94, minimum 25.00, maximum 72.03; NAWM: median (43.33 (CI 28.26, 52.00), 25% percentile 29.41, 75% percentile 51.36, minimum 27.78, maximum 64.00; CAL: median 40.54 (CI 26.53, 59.21), 25% percentile 32.64, 75% percentile 54.57, minimum 26.53, maximum 59.21). Data were analyzed by linear mixed-effects models followed by ANOVA to determine main effects and Tukey post-hoc pairwise comparisons. Each data point represents the average quantification of 5–10 different regions of interest from the same case (n = 10 controls (5 M, 5 F), n = 11 MS (5 M, 6 F)). AL active lesion, CAL chronic active lesion, CIL chronic inactive lesion, NAWM normal-appearing white matter, WM white matter from control donors. Source data are provided as a Source Data file.