Abstract

Increased protein levels of striatal-enriched tyrosine phosphatase (STEP) have recently been reported in postmortem schizophrenic cortex. The present study sought to replicate this finding in a separate cohort of postmortem samples and to extend observations to striatum, including subjects with bipolar disorder and major depressive disorder in the analysis. No statistically significant changes between disease and control subjects were found in STEP mRNA or protein levels in dorsolateral prefrontal cortex or associative striatum. Although samples were matched for several covariates, postmortem interval correlated negatively with STEP protein levels, emphasizing the importance of including these analyses in postmortem studies.

Highlights

  • Striatal-enriched tyrosine phosphatase (STEP) is a brain-specific, developmentally regulated tyrosine phosphatase

  • As these samples had been used in a microarray analysis previously (GEO Dataset GSE53987), the probe sets for STEP were examined in both prefrontal cortex (PFC) and STR

  • As has been demonstrated in multiple other postmortem schizophrenic cohorts [10,11,12,13,14], a significant disease-associated reduction in parvalbumin mRNA was measured in pre-frontal cortex (Fig. B in S1 File, F = 16.25, p

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Summary

Introduction

Striatal-enriched tyrosine phosphatase (STEP) is a brain-specific, developmentally regulated tyrosine phosphatase. The substrates of STEP include the GluR2 subunit of the AMPA [2] and the NR2B subunit of the NMDA receptor [3], and position STEP as a downstream negative regulator of glutamate receptor signaling. Transcriptional profiling of STEP KO mice has provided additional support for the role of STEP in the NMDA signaling pathway [4]. Given the NMDA hypofunction hypothesis of schizophrenia [6, 7], increased STEP activity would be hypothesized to reduce functional NMDA signaling.

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