Figure 2.

P7C3 Corrects Morphological and Electrophysiological Deficits in npas3^−/− DG. A) Golgi-Cox staining of the DG revealed aberrant dendritic arborization in npas3^−/− mice relative to wild-type littermates (ten sections from each of five mice in each group). In addition to reduced dendritic length and branching, npas3^−/− DG granular neurons also exhibited significantly reduced spine density relative to wild-type littermates (∗p < 0.00001, Student’s t test). The top lower-power micrographs of DG were taken at the same magnification (scale bar, 200 μm). For the bottom two higher-power micrographs of dendritic spines, scale bar is 10 μM. B) In hippocampal slice preparation from npas3^−/− mice, synaptic transmission, as assessed by whole-field recordings of fEPSPs, was increased both in the outer molecular layer of the DG and the CA1 region of the hippocampus relative to that of wild-type mice. C) Golgi-Cox staining of DG granular neurons showed that prolonged daily treatment of npas3^−/− mice with P7C3 enhanced dendritic arborization. Results shown are representative of ten sections from each of five mice in each group. Higher-power micrographs are shown on top (scale bar, 25 μm), and a lower-power micrograph illustrating the entire granular layer of the DG is shown below (scale bar, 200 μm). D) Prolonged administration of P7C3 normalized whole field recordings of fEPSPs in the DG but not the CA1 region of npas3^−/− mice. In all graphs, data are expressed as mean ± SEM. (Reprinted from Cell, 142(1), Pieper et al., Discovery of a Proneurogenic, Neuroprotective Chemical, 39–51, 2010, with permission from Elsevier)