Fig. 5: Administered kCP enters in the brain of cpKO mice inducing improvement in motor coordination, reduction of iron accumulation and prevention of cerebellar neurodegeneration.

a Ex vivo distribution of [⁶⁴Cu]-kCP measured in the brain of cpKO (N = 9) and control WT (N = 6) mice. Data are expressed as Standardized Uptake Value (SUV) and are the means ± SEM. b–d Motor coordination behavior analysis for b constant speed rotarod, c grid test, and d beam walking test in mice after 4 months of treatment with either kCP (KO+kCP) or saline (KO, WT). e ELISA evaluation of human CP in brain of treated mice. f Iron quantification by ICP-MS in whole brain homogenates. g Representative images of iron staining (brown) in choroid plexus where cells were counterstained in blue; gray-scale lower panels represent the originally acquired images for different wavelengths corresponding to blue and brown; magnification 20×, scalebar: 50 µm. h Quantification of iron deposition as ratio of iron/cells-stained areas. i Purkinje cells count on a linear distance of 500 µm in the cerebellum of treated mice. j Representative images of the staining of Purkinje cells; magnification 10×, scalebar: 50 µm. Data are presented as means ± SEM; each dot corresponds to one animal (N = 20 mice/group and N = 40 for cpKO at 6 months). Statistical P values were evaluated by Mann-Whitney test in a, by one-way ANOVA (An) followed by Tukey’s post-test analysis c, d, h, i or Kruskal-Wallis (K-W) test followed by either Dunn’s b or uncorrected Dunn’s e, f post-test analysis. k Representative confocal images of autofluorescent Purkinje cells. Scalebar: 10 µm. l Analysis of autofluorescent Purkinje cells linear density (KO N = 10, KO + CP N = 12, WT N = 12 mice/group). Data are presented as means ± SEM; each dot corresponds to one animal. Statistical P values were evaluated by one way ANOVA followed by Newman Keuls post-test.