Figure 7

Systemic 5-FU treatment causes delayed dysregulation of Olig2 expression in oligodendrocytes in the CC. Animals were treated with 5-FU as in Figure 3 and analyzed for expression of Olig2 in the CC at various time points. There was a marked reduction in the number of such cells at 56 days ((a) control; (b) 5-FU) after completion of treatment, but not at 1 or 14 days after treatment. (c) Percent-corrected number of Olig2⁺ cells in the CC at day 1 and day 56 post-treatment with 5-FU, normalized to control values at each time point. Data represent averages from three animals in each group, shown as mean ± s.e.m (*p < 0.001, one-way ANOVA) in comparison with control values at each time point. The scale bar represents 150 μm. (d-i) Representative confocal micrographs showing loss of Olig2 expression in a subset of CC1⁺ oligodendrocytes in the CC of a 5-FU-treated animal at day 56 in comparison with a sham-treated animal at the same time point. The reduction in numbers of Olig2⁺ cells seen at day 56 after treatment was not associated with an equivalent fall in oligodendrocyte numbers, as determined by analysis of CC1⁺ expression. (d-f) In control animals, there is a close equivalence between CC1 expression (d) and Olig2 expression (e); a merged image is shown in (f). Three Olig2⁺ CC1^- cells can be seen in (e,f) (arrowheads), which are probably O-2A/OPCs. (g-i) In contrast, in 5-FU-treated animals there is a reduction in the number of Olig2⁺ cells (h), but the CC of these animals contains many CC1⁺ cells (g) that do not express Olig2 (i) (arrows, Olig2⁺ CC1⁺; arrowheads, Olig2⁺ CC1^- cells). The scale bar represents 25 μm.