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

J Affect Disord. 2012 Jan;136(1-2):185-188. doi: 10.1016/j.jad.2011.09.024. Epub 2011 Oct 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Autopsy
  • Depressive Disorder, Major / metabolism*
  • Female
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / metabolism*
  • Rats
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3