Fig. 1.

Cyclopamine prevents the electroconvulsive seizure-mediated increase in the proliferation of dentate granule cell progenitors. Rats received i.c.v. administration of either vehicle or cyclopamine through osmotic minipumps prior to the administration of sham or electroconvulsive seizure (ECS) treatment, as described in Materials and methods. The number of proliferating progenitors within the subgranular zone (SGZ)/granule cell layer (GCL) of the dentate gyrus was determined using the mitotic marker BrdU. ECS administration resulted in a significant increase in the number of BrdU-positive cells per section within the dentate gyrus of the vehicle + ECS group (B; *P < 0.001 as compared with the Vehicle + Sham treatment). Cyclopamine pretreatment significantly reduced the number of BrdU-positive cells per section in the Cyclopamine + Sham group (B; *P < 0.001 as compared with the Vehicle + Sham treatment group). ECS administration to animals pretreated with cyclopamine (Cyclopamine + ECS group; B) did not significantly increase the number of BrdU-positive cells within the dentate gyrus as compared with the Cyclopamine + Sham treatment, indicating that cyclopamine prevents the ability of ECS to enhance the proliferation of dentate granule cell progenitors. The Cyclopamine + ECS group had significantly decreased numbers of BrdU-positive cells per section as compared with the Vehicle + ECS group (δP < 0.001; B). Shown are representative images of the dentate gyrus region from Vehicle + Sham, Vehicle + ECS, Cyclopamine + Sham and Cyclopamine + ECS groups (A). BrdU-positive cells (arrow A) were observed in the SGZ, at the border of the hilus (H) and the GCL. The results are expressed as the mean ± SEM (n = 5 per group) number of BrdU-positive cells per section in the dentate gyrus. *P < 0.001 indicates significantly different from Vehicle + Sham; δP < 0.001 indicates significantly different from Vehicle + ECS (ANOVA and Bonferroni post-hoc test).