Fig. 6.

Validation of Myelination Index and model for cerebellar slices. A) The Myelination Index increases linearly between 4 days in vitro and 12 days in vitro, showing that this method is sensitive enough to detect changes in amount of myelin. *p < 0.01, ANOVA and Dunnett's Multiple Comparison Test. (N = 2 experiments, a minimum of 7 slices counted per condition.) B) Factors previously used to try and alter remyelination were added to the culture medium 24 h after demyelination, and remyelination assessed 14 days after. The data is normalised to the control (no additive) data. Fibroblast growth factor (FGF), Platelet Derived Growth Factor (PDGF), Neuregulin 1 (NRG1), NRG1-III and DAPT (gamma secretase inhibitor) addition showed no difference compared to the controls (control — no additive, PBS added, DMSO added). However, 9 cis-retinoic acid (9cRA) significantly enhances remyelination, and its antagonist PA452 significantly inhibits remyelination. Specific agonists of the RXR receptor, HX630 and PA024 also enhance myelination and this effect is reversed by the use of the antagonist PA452 (Mean + S.D., * p < 0.05 in comparison to control, ANOVA and Dunnett's Multiple Comparison Test) (N = 3 experiments, a minimum of 7 slices counted per condition). This is in concordance with in vivo remyelination experiments after demyelination with a myelin toxin in rodents (see Table 1).