Fig. 5.

Haloperidol and Clozapine revert demyelination events in ex vivo MS model. The demyelinating agent LPC causes MBP loss in MG cultures (A). This feature is abolished by cotreating cells with the autophagy inhibitors haloperidol (Halo) and clozapine (Cloz). Similar to proinflammatory cytokines, LPC boosts autophagy (B), causes mitochondrial function impairment (C), and activates mitochondrial autophagy (D). Calculated values of the Seahorse assay are reported in SI Appendix, Fig. S5. (E) Ex vivo analysis performed in OSC confirms the ability of the antipsychotic agents Halo and Cloz to improve myelinization following LPC treatment. (F) Fluorescence shape (myelin roundness) and colocalization between MBP (red) and the neuronal marker β-tubulin III (green). Immunoblots are representative of at least three independent experiments. Quantification of the Western blot performed is reported in SI Appendix, Table S1. The graphs in C, E, and F represent the mean ± SD of five experiments; two-way ANOVA with Dunnett’s multiple comparison test, ****P < 0.0001, ***P < 0.001, **P < 0.01.