Figure 4.

MeCP2 depletion at different advanced adult ages leads to rapid and severe reduction in the dendritic complexity of hippocampal pyramidal neurons. (A and B) Sholl analysis of CA1 pyramidal neurons of the symptomatic 15 W- (A) and 20 W- (B) Tam-injected Mecp2^loxJ/CreER mice shows that the basal dendrites of CA1 pyramidal neurons are significantly less complex than those of the Veh-injected Mecp2^loxJ/CreER age-matched littermate mice. Two-way repeated-measures ANOVA followed by appropriate post hoc for multiple-comparisons test was used to determine differences within Veh- and Tam-injected groups. Error bars are mean ± SEM. *P < 0.05. (C–F) Branch analyses of the CA1 pyramidal neurons of the symptomatic 15 W- (C and D) and 20 W- (E and F) Tam-injected Mecp2^loxJ/CreER male mice exhibit shorter basal dendritic branch length (C and E) and fewer numbers of nodes (D and F). t-test was used to compare between Veh- and Tam-injected animals of each age groups. Error bars are mean ± SEM. **P < 0.01. (G–J) CA1 pyramidal neurons of the symptomatic 15 W- (G and H) and 20 W- (I and J) Tam-injected Mecp2^loxJ/CreER male mice exhibit structural abnormalities in dendritic spines and reduced spine density. Representative images of dendrites of CA1 pyramidal neurons showing structural abnormalities in dendritic spines of symptomatic 15 W- (G) and 20 W- (I) Tam-injected Mecp2^loxJ/CreER male mice when compared with that of the Veh-injected mice. Scale bars, 2 µm. CA1 pyramidal neurons of 15 W- (H) and 20 W- (J) Tam-injected Mecp2^loxJ/CreER mice demonstrate significant reduction in dendritic spine density. Spine density per 100 µm length was measured on secondary dendrites. t-test was used to compare within Veh- and Tam-injected animals of each age groups. Error bars are mean ± SEM. *P < 0.05. n = 4 mice per genotype and age. n = 12 neurons per animal for all dendritic and spine analyses.