Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders.
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 compared the density of immunoreactive cells of the STG (BA22) from 11 schizophrenia patients with those from 11 age- and sex-matched controls, and found significantly lower densities of DARPP-32-immunoreactive (IR) cells and threonine (Thr) 34-phosphorylated DARPP-32-IR cells in the STG in the schizophrenia group.
These results suggest that the decrease in DARPP-32 in schizophrenia was more marked in neurons of DLPFC than in other cells or other brain regions, and that this decrease might be partly compensated for by an increase in expression of Thr34-phosphorylated DARPP-32 in DLPFC.
our data suggest: (i) C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 are important in the pathogenesis of schizophrenia and bipolar disorder; (ii) these two disorders share common disease-related mechanisms linked to dopamine signalling; (iii) the expression of these genes is closely correlated; and (iv) DRD2 provides the initial trigger in the pathogenesis of these disorders.