Figure 4.
Prolonged, 1 month infusion of rapamycin reduced aberrant Timm staining. Timm stained dentate gyrus in vehicle-infused (A) and contralateral noninfused (B) hippocampus and in 10 mm rapamycin-infused (C) and contralateral noninfused (D) hippocampus. Asterisks indicate infusion sites (A, C). g, Granule cell layer; m, molecular layer; h, hilus; CA3, CA3 pyramidal cell layer. E, Higher-magnification views reveal less aberrant Timm staining in rapamycin-infused regions. E1, Vehicle-infused hippocampus (arrow in A). E2, Rapamycin-infused hippocampus at septotemporal level of cannula (arrow in C). E3, Rapamycin-infused hippocampus at 180 μm toward temporal pole of hippocampus from section shown in C and E2. E4, Contralateral noninfused hippocampus (arrow in D). F, The average percentage of area of the granule cell layer (gcl) + molecular layer (ml) that is Timm positive versus section position along the septotemporal axis relative to infusion site in rats infused with 10 mm rapamycin (n = 8). Infusion site = 0. The septal pole is to the left (negative values). The temporal pole is to the right (positive values). G, Difference in the percentage of the granule cell layer + molecular layer that is Timm positive in infused minus contralateral noninfused hippocampi. Negative values indicate reduced aberrant Timm staining in infused hippocampi. Values calculated in individual animals by averaging results of the three sections closest to the infusion site (between dashed vertical lines in F) and corresponding sections in the contralateral hippocampus. Hippocampi infused with 10 mm (n = 8), 1 mm (n = 4), and 0.1 mm (n = 3) rapamycin displayed less aberrant Timm staining than those infused with 0.01 mm rapamycin (n = 4) or vehicle alone (n = 6) (*p < 0.05, ANOVA with Bonferroni t test). Error bars indicate SEM.