Glycogen synthase kinase-3β, β-catenin, and tau in postmortem bipolar brain

Therapeutic concentrations of the anti-bipolar drug lithium inhibit the activity of glycogen synthase kinase-3 beta, which raises the possibility that this enzyme and its substrates may be altered in the brain of subjects with bipolar disorder. Therefore, in prefrontal cortical samples from subjects with bipolar disorder and age-matched control subjects, we examined the levels of glycogen synthase kinase 3 beta and of two proteins modified by it, beta-catenin and the microtubule associated protein tau. There were no significant differences between subject groups among these measurements, but there was a tendency for the tau isoform profile to be modified in bipolar tissue. Thus, while there are no differences between bipolars and controls in prefrontal cortical levels of glycogen synthase kinase-3 beta, beta-catenin, or tau, tau isoform levels or phosphorylation states may be modified in bipolar disorder.