Fig. 3.

Paroxetine enhances proliferation of neural progenitor cells (NPC). (a, b) Human NPC were cultured in proliferation medium on poly-D-lysine coated cover slips and treated with paroxetine for 24 hours and with BrdU reagent overnight. (a) BrdU incorporation was determined by immunostaining (red fluorescence). DIC images were also taken to count total number of cells. (b) Quantification shows significant proliferation at 2 μM paroxetine. Data represents two independent experiments performed with duplicate wells at each dosage. An analysis of variance showed that the effect of paroxetine was significant F[3, 19] = 19.41, p < 0.0001). Post hoc analysis was done using Tukey’s multiple comparison test. Values represent mean ± SEM (3 experiments per condition, ***p < 0.001). (c, d) gp120 transgenic mice were implanted with either saline- or paroxetine-containing pumps for 28 days and were analyzed 2 hours after BrdU injection. (c) Representative images of cells labeled with BrdU to identify proliferative cells (BrdU+, in red). Scale bar = 200 μm. SGZ, subgranular zone. GCL, granule cell layer. (#) quantification of proliferating hippocampal cells show that paroxetine administration increased NPC proliferation in gp120 transgenic mice. An analysis of variance showed that the effect of paroxetine was significant: F[3, 37] = 9.92, p < 0.0001). Post hoc analyses were done using Tukey’s multiple comparison test. Values represent mean ± SEM (n =5 ~ 6 per group, ***p < 0.001). (e). Mice were administered daily injections of BrdU (50 mg/kg) for seven days, beginning 2 weeks after pump implantation, and analyzed 28 days after the first BrdU injection. Quantification of newly generated (BrdU + NeuN+) neurons by analysis of variance (F[2, 9] = 0.0088) shows the rescue of adult hippocampal neurogenesis in gp120 transgenic mice by paroxetine. Values represent mean ± SEM (n =5 ~ 6 per group, *p <0.05, one-way ANOVA followed by Tukey’s multiple comparison test)