Fig. 3: Testosterone and DHT induce a potent regeneration of myelin in female mice.

a Scheme of the experimental protocol. b–g Visualization of OPC proliferation in (b, c), OPC differentiation in (d, e) and MBP expression in (f, g) evaluated 7 days after LPC injection into the corpus callosum of ovariectomized females daily treated with the drug vehicle (Veh), testosterone (T) or dihydrotestosterone (DHT). In (b), the white arrows indicate Ki67⁺ PDGFRα⁺ proliferating OPCs. h–k Immunostaining of local inflammatory cells using Iba1 and Arg-1 antibodies for the detection of the microglial population and the cell subset expressing the anti-inflammatory marker Arg-1 in (h, i) as well as GFAP and STAT3 antibodies, as markers of astrocytes and their reactive state in (j, k). The dashed lines in (d, f, h, j) indicate the lesion. The boxed area in (f, j) is magnified in the inset. Scale bars: 50 µm unless indicated. Data in (c, e, g, i, k) are presented as mean values ± SEM from n = 8 mice/group examined over 2 independent experiments (3–5 slices/animal). l–o Scheme of the experimental protocol in (l). Electron microscopy analysis of the spinal cords from Vehicle and DHT-treated EAE females in (m) and determination of the g-ratio values plotted according to axon diameter in (n; 100 axons per animal, n = 3/group) as well as the mean value of g-ratios in each group in (o; 100 axons per animal, n = 3 mice/group). The upper, middle and lower horizontal lines of the boxplots represent the upper, median and lower quartile, respectively. Whiskers depict the smallest or largest values within 1.5-fold of the interquartile range. P values were calculated by using the one-way ANOVA test together with Tukey’s (c, i, k) or Holm-Sidak’s (g) multiple comparisons test, Kruskal-Wallis test together with Dunn’s.multiple comparisons test e, two-tailed Mann-Whitney test (o). Brown-Forsythe correction was used for (e left, i left, k right). **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001 compared to the control (Veh). ##p = 0.0049 compared to the indicated condition. Source data are provided as a Source Data file.