Fig. 5.
M1 potentiation increases both Gsk3β inhibition and synaptic NMDAR levels in the brainstem of Mecp2+/- mice. A Representative Western blots from the brainstem of Mecp2+/+ and Mecp2+/- mice treated with vehicle or VU595. B–C Neither the inhibition (S21) nor the activation (Y279) sites on Gsk3α were significantly impacted by treatment with VU595 as measured by the ratio of phosphorylated (P) to total (T) protein. D Administration of VU595 significantly increased the P/T ratio at the S9 inhibitory site of Gsk3β, specifically in the brainstem of Mecp2+/- mice, while having no impact in Mecp2+/+ mice. Two-way ANOVA with Tukey post hoc analysis. E The activation site (Y216) of Gsk3β was not affected in the brainstem by VU595 treatment, regardless of genotype. F Representative synaptosome Western blots from the brainstem of Mecp2+/+ and Mecp2+/- mice treated with vehicle or VU595. G VU595 significantly increased the presence of NR2a/b containing NMDARs at the synapse of Mecp2+/- mice while having no impact on Mecp2+/+ control mice. Two-way ANOVA with Tukey post hoc analysis. H PSD-95 control Western blots confirm that synaptosomes assessed in these experiments contained postsynaptic structures in equivalent amounts across treatments and genotypes. *p < 0.05, ***p < 0.001