Figure 3.

Quantification of the impact of simvastatin on OPCs in the corpus callosum. A, B: Coronal sections of corpus callosum of normal animals on normal diet. OPCs (small arrowheads) were identified as having strong staining for the transcription factors Olig2 and Nkx2.2 and showed a random distribution pattern (brown). Weakly positive cells (large arrowheads) were taken to be mature OLGs and were aligned in rows. Nuclei were labeled with hematoxylin (blue). Scale bar = 25 μm. C: Average numbers of Olig2^strong OPCs per mm² medial corpus callosum (CC) ± SEM. Simvastatin treatment (Simva) (weeks 4 to 6) of animals on normal diet (black bars) caused a significant increase in Olig2^strong OPCs relative to vehicle control. Cuprizone administration (gray bars) resulted in an increase in Olig2^strong cells at this time. Simvastatin treatment during weeks 4 to 6 inhibited this increase in Olig2^strong OPCs in the CC. At week 9, vehicle treated animals on normal diet (black bars) show an increase in Olig2^strong cells compared with week 6. At this time point, simvastatin treatment of animals on normal diet had no significant effect on numbers of Olig2^strong OPCs. Cuprizone-treated animals showed a decrease in these cells by week 9 relative to week 6. However, simvastatin treatment during weeks 4 to 9 or 7 to 9 caused a significant increase in Olig2^strong OPCs in the CC relative to cuprizone alone. D: Average numbers of Nkx2.2^strong OPCs per mm² medial CC ± SEM. Simvastatin treatment (weeks 4 to 6) of animals on normal diet (black bars) caused a significant increase in Nkx2.2^strong cells in comparison with control (vehicle + normal diet). Simvastatin treatment (weeks 4 to 6) of animals on cuprizone (gray bars) was associated with a decrease in Nkx2.2^strong OPCs in the CC versus control (cuprizone + vehicle). By week 9, vehicle treated animals on normal diet (black bars) showed a decrease in Nkx2.2^strong cells compared with week 6. At this time point, simvastatin treatment of animals on normal diet caused an increase in numbers of Nkx2.2^strong OPCs. Cuprizone administration induced a significant increase in Nkx2.2^strong OPCs by week 9. Simvastatin treatment (weeks 4 to 9) of animals on cuprizone caused a significant decrease in numbers of Nkx2.2^strong OPCs in the CC relative to cuprizone alone. Analysis of variance P values <0.001. ns P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001.