Figure 8.

Effect of intracerebroventricular (ICV) administration of 12-deoxyphorbols on hippocampal neurogenesis. Mice received single unilateral ICV injections of prostratin, ER271, ER272 or vehicle, and peritoneal injections of bromodeoxyuridine (BrdU) to label proliferating cells, as described in Methods. Photomicrographs show adult mouse brain coronal sections containing the dentate gyrus of the hippocampus (DG). Left (A, D, G, J) and middle (B, E, H, K) column photomicrographs show contralateral and ipsilateral brain sections, respectively, processed for immunohistochemical detection of BrdU to label proliferating neural progenitor cells (NPCs); black arrows point to newly divided cells in the DG. Right column photomicrographs (C, F, I, L) show ipsilateral sections processed for double immunofluorescence detection of BrdU and doublecortin (DCX), the latter being a cell marker for immature newly formed neurons; white arrows point to BrdU/DCX double-labeled cells, which represent a subpopulation of proliferating BrdU⁺ cells that are already committed to neuronal differentiation. (A-C) Vehicle-injected control mice. (D-F) Mice injected with ER272. (G-I) Mice injected with ER271. (J-L) Mice injected with prostratin. (M) Quantification of BrdU⁺ nuclei within the DG of mice that had received ICV injections of the indicated drugs; left bars correspond to the injected side of the brain (ipsilateral) and right bars correspond to the noninjected side of the brain (contralateral). (N) Quantification of the percentage of BrdU⁺ cells that express the early neuronal marker DCX in the ipsilateral (left bars) or contralateral (right bars) side of the injection. contra, contralateral hemisphere; ipsi, ipsilateral hemisphere. #P<.05 when comparing ipsilateral vs contralateral sides in a Student’s t test; *P<.05 when comparing different treatments with control ipsilateral in 1-way ANOVA test; †P<.05 when comparing different treatments with control contralateral in 1-way ANOVA test. Scale bar = 200 μm.