GSK3β inhibition restores cortical gamma oscillation and cognitive behavior in a mouse model of NMDA receptor hypofunction relevant to schizophrenia

摘要

Immunoreactivity levels in the somata of cortical PV neuron against GSK3α, GSK3β, or phopshorylated-Y216-GSK3β (Y279-GSK3α). Normalized by the average levels of each immunoreactivity (IR) of the non-PV (pyramidal) neurons, and are shown by the level of floxed-Grin1 control non-PV neurons as 100%. Although there was no difference in GSK3α (a) and GSK3β expression levels (b), the levels of phosphorylated GSK3 at Tyrosine residues (c) were increased in the PV neurons of Grin1 mutant mice (p = 1.01E–04, t test), suggesting over-activation of GSK3 in the NMDAR-deleted PV neurons. The number of brain sections obtained from three mice (8–10 week-old, both sexes) per genotype/immunostaining is shown in bar graph. Panels D and E show the images of GSK3 phospho-Tyr immunoreactivity (IR) (Left) and PV-IR (right) of floxed-Grin1 control mice (d) and mutant mice (e). Note that GSK3β phospho-Y216 antibody cross-reacts with phospho-Y279 in GSK3α. Arrowheads show cells for double-positive for phosho-Tyr-GSK3 and PV. **p < 0.01.