Protein levels of β-catenin and activation state of glycogen synthase kinase-3β in major depression. A study with postmortem prefrontal cortex

Background t/GSK3β signaling pathway was implicated in mood disorders. Beta-catenin is a protein targeted by this signaling axis. We aimed to examine whether there is an abnormality in this signaling axis in major depression. s rtem brains from 20 depressed and 20 non-depressed subjects were used. In both groups, suicide and non-suicide were included in equal number. Protein levels of β-catenin, tGSK3β and ser9-pGSK3β were determined in prefrontal cortex. s yielded significant variations between groups in β-catenin (F3,36 = 19.5; p < 0.001) and pGSK3β protein (F3,36 = 14.3; p < 0.001) and in tGSK3β-to-pGSK3β ratio (F3,36 = 10.9; p < 0.001). Fisher tests showed decrease in both groups of MDD and MDD with suicide (MDD + S) for β-catenin (p < 0.001) and pGSK3β levels (p < 0.001) respectively. The tGSK3β-to-pGSK3β ratio was increased in MDD and MDD + S subjects (p < 0.001). A negative correlation was observed between β-catenin levels and the activation state of the GSK3β (r2 = 0.358; p < 0.005). tions mple was small and only a fraction of s9-pGSK3β, albeit significant, was used and; the mood state at the time of death was unknown. sions udy observed a dysregulation of Wnt/GSK3β signaling associated with a lifetime of major depression. The study may have relevance in further development of drugs based on GSK3β inhibition.