TY  - JOUR
PY  - 2012//
TI  - Protein levels of β-catenin and activation state of glycogen synthase kinase-3β in major depression. A study with postmortem prefrontal cortex
JO  - Journal of affective disorders
A1  - Karege, Felicien
A1  - Perroud, Nader
A1  - Burkhardt, Sandra
A1  - Fernandez, Rafael
A1  - Ballmann, Eladia
A1  - La Harpe, Romano
A1  - Malafosse, Alain
SP  - 185
EP  - 188
VL  - 136
IS  - 1-2
N2  - 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>
LA  - en
SN  - 0165-0327
UR  - http://dx.doi.org/10.1016/j.jad.2011.09.024
ID  - ref1
ER  -