SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia.

M Udawela,T T Money,E Scarr,I P Everall,B Dean,M S Seo,J Neo

doi:10.1038/tp.2015.108

M Udawela, T T Money + Show 5 more

Open Access

PDF Available

https://doi.org/10.1038/tp.2015.108

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

Selenium binding protein 1 (SELENBP1) messenger RNA (mRNA) has previously been shown to be upregulated in the brain and blood from subjects with schizophrenia. We aimed to validate these findings in a new cohort using real-time PCR in Brodmann's Area (BA) 9, and to determine the disease specificity of increased SELENBP1 expression by measuring SELENBP1 mRNA in subjects with major depressive disorder and bipolar disorder. We then extended the study to include other cortical regions such as BA8 and BA44. SELENBP1 mRNA was higher in BA9 (P=0.001), BA8 (P=0.003) and BA44 (P=0.0007) from subjects with schizophrenia. Conversely, in affective disorders, there was no significant difference in SELENBP1 mRNA in BA9 (P=0.67), suggesting that the upregulation may be diagnosis specific. Measurement of SELENBP1 protein levels showed that changes in mRNA did not translate to changes in protein. In addition, chronic treatment of rats with antipsychotics did not significantly affect the expression of Selenbp1 in the cortex (P=0.24). Our data show that elevated SELENBP1 transcript expression is widespread throughout the prefrontal cortex in schizophrenia, and confirm that this change is a consistent feature of schizophrenia and not a simple drug effect.

Highlights

Levels of selenium (Se) binding protein 1 (SELENBP1) expression have been shown to be higher in the dorsolateral prefrontal cortex from subjects with schizophrenia,[1,2] with the second study showing higher levels of SELENBP1 messenger RNA in the dorsolateral prefrontal cortex from subjects with bipolar disorder (BP) who had psychosis,[2] leading the authors to suggest that increased SELENBP1 expression may be associated with a psychotic state rather than a diagnostic criterion
We addressed the extent of changes in cortical SELENBP1 expression by measuring messenger RNA (mRNA) levels in multiple cortical regions, determined whether a two-marker haplotype of SELENBP1, previously shown to be nominally associated with risk for schizophrenia,[9] influenced brain SELENBP1 expression, and whether changes in SELENBP1 mRNA translated to changes in protein levels
There were no significant differences in mean age (P = 0.91), post-mortem interval (P = 0.48), RNA integrity number (P = 0.52 BA9, P = 0.92 BA44 and P = 0.74 BA8), brain hemisphere (χ21 = 2.07, P = 0.15) or sex ratio (χ21 = 0.0, P = 1) between subjects with schizophrenia and controls (Table 1)

Summary

Introduction

Levels of selenium (Se) binding protein 1 (SELENBP1) expression have been shown to be higher in the dorsolateral prefrontal cortex from subjects with schizophrenia,[1,2] with the second study showing higher levels of SELENBP1 messenger RNA (mRNA) in the dorsolateral prefrontal cortex from subjects with bipolar disorder (BP) who had psychosis,[2] leading the authors to suggest that increased SELENBP1 expression may be associated with a psychotic state rather than a diagnostic criterion. The role of SELENBP1 in the central nervous system (CNS) remains largely unknown, there is evidence to suggest it may be involved in neurite growth and remodelling.[3] Given that dendritic and synaptic proteins are altered in BP and schizophrenia,[4,5,6,7,8] SELENBP1 may have a role in the aetiology of these disorders. To challenge this hypothesis, we investigated whether SELENBP1 is differentially expressed in the cortex from subjects with schizophrenia, BP or major depressive disorder (MDD). We determined whether CNS Selenbp[1] expression was altered by chronic exposure to antipsychotic drugs to determine whether changes in the expression of that gene could be involved in their mechanism of action

Objectives

Methods

Results