%0 Journal Article
%T Protein levels of β-catenin and activation state of glycogen synthase kinase-3β in major depression. A study with postmortem prefrontal cortex
%J Journal of affective disorders
%D 2012
%A Karege, Felicien
%A Perroud, Nader
%A Burkhardt, Sandra
%A Fernandez, Rafael
%A Ballmann, Eladia
%A La Harpe, Romano
%A Malafosse, Alain
%V 136
%N 1-2
%P 185-188
%X BACKGROUND: The Wnt/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. METHODS: Postmortem 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 ser(9)-pGSK3β were determined in prefrontal cortex. RESULTS: ANOVA yielded significant variations between groups in β-catenin (F(3,36)=19.5; p<0.001) and pGSK3β protein (F(3,36)=14.3; p<0.001) and in tGSK3β-to-pGSK3β ratio (F(3,36)=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). LIMITATIONS: The sample was small and only a fraction of s(9)-pGSK3β, albeit significant, was used and; the mood state at the time of death was unknown. CONCLUSIONS: The study 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.<p /><p>Language: en</p>
%G en
%I Elsevier Publishing
%@ 0165-0327
%U http://dx.doi.org/10.1016/j.jad.2011.09.024