Elevated postmortem striatal t-DARPP expression in schizophrenia and associations with DRD2/ANKK1 polymorphism

Abstract

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN) have been implicated in the pathogenesis of schizophrenia because they function as molecular integrators of dopamine and glutamate signaling. DARPP-32 and CaN are mainly expressed in the caudate nucleus and putamen; however, a few postmortem brain studies have focused on DARPP-32 expression in striatum from patients with schizophrenia. We used immunoblotting techniques and postmortem tissue samples from patients with schizophrenia and from normal control individuals to examine the expression of two major DARPP-32 isoforms, full-length (FL-DARPP) and truncated (t-DARPP), and of CaN in the striatum. We also assessed whether there was any significant correlation between the expression levels of either protein and the A1 allele of Taq1A genotype in the dopamine D2 receptor (DRD2) gene/ankyrin-repeat containing kinase 1 (ANKK1) gene. We found that the mean t-DARPP expression level in the caudate was higher in patients with schizophrenia than in control individuals (P<0.05) and the A1 allele of Taq1A genotype in DRD2/ANKK1 was significantly associated with elevated expression of t-DARPP in the caudate. Also, the A1 allele was significantly correlated with the total score of antemortem psychiatric symptoms. These results may reflect potential molecular mechanisms important to the pathogenesis of schizophrenia.