Reduced GSK-3β mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients

Summary.

Glycogen Synthase Kinase (GSK)-3 is a ubiquitous serine/threonine protein kinase highly abundant in brain which plays a key role in neural development and neuron survival. We have previously reported that GSK-3β protein levels and GSK-3 activity are reduced by over 40% in postmortem prefrontal cortex of schizophrenic patients compared to patients with bipolar illness, unipolar depression and to normal controls, and Emamian et al. have recently presented convergent evidence for impaired AKT1-GSK-3β signaling in schizophrenia. Using specimens of dorsolateral prefrontal cortex tissue obtained from The Stanley Medical Research Institute’s Brain Collection, from the same subjects used previously, we now show that GSK-3β, but not GSK-3α, mRNA levels are 36% lower in the patients with schizophrenia compared to all other comparison groups. The present study lends further support to the finding of low GSK-3β levels in schizophrenia and extends this observation by suggesting that the decrease in GSK-3β may be due to reduced protein synthesis possibly due to altered transcriptional drive of the GSK-3β gene.