Dataset Information

SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia.

ABSTRACT: 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.

SUBMITTER: Udawela M

PROVIDER: S-EPMC4564563 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia.

Udawela M M Money T T TT Neo J J Seo M S MS Scarr E E Dean B B Everall I P IP

Translational psychiatry 20150804

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 an ...[more]

PMID: 26241353

Similar Datasets

Project description:Because of the role played by miRNAs in post-transcriptional regulation of an array of genes, their impact in neuropsychiatric disease pathophysiology has increasingly been evident. In the present study, we assessed microRNA expression in prefrontal cortex (Brodmann area 10) of a well-characterized cohort of major depressed, bipolar, and schizophrenia subjects (obtained from Stanley Neuropathology Consortium; n = 15 in each group), using high throughput RT-PCR plates. Discrete miRNA alterations were observed in all disorders, as well as in suicide subjects (pooled across diagnostic categories) compared to all non-suicide subjects. The changes in the schizophrenia group were partially similar to those in the bipolar group, but distinct from changes in depression and suicide. Intriguingly, those miRNAs which were down-regulated in the schizophrenia group tended to be synaptically enriched, whereas up-regulated miRNAs tended not to be. To follow this up, we purified synaptosomes from pooled samples of the schizophrenia vs. control groups and subjected them to Illumina deep sequencing. There was a significant loss of small RNA expression in schizophrenia synaptosomes only for certain sequence lengths within the miRNA range. Moreover, 73 miRNAs were significantly down-regulated whereas only one was up-regulated. Strikingly, across all expressed miRNAs in synaptosomes, there was a significant inverse correlation between the fold-change of a given miRNA seen in schizophrenia and its synaptic enrichment ratio observed in controls. Thus, synaptic miRNAs tended to be down-regulated in schizophrenia, and the more highly synaptically enriched miRNAs tended to show greater down-regulation. These findings point to some deficit in miRNA biogenesis, transport, processing or turnover in schizophrenia that is selective for the synaptic compartment. A novel class of ncRNA-derived small RNAs, shown to be strongly induced during an early phase of learning in mouse, is also expressed in man, and at least one representative (SNORD85) was strongly down-regulated in schizophrenia synaptosomes.

Project description:In subjects with schizophrenia, impairments in working memory are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction appears to be due, at least in part, to abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory circuitry. To test the hypothesis that altered GABA-mediated circuitry in the DLPFC of subjects with schizophrenia reflects expression changes of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission, we conducted a systematic expression analysis of GABA-related transcripts in the DLPFC of 14 pairs of schizophrenia and age-, sex- and post-mortem interval-matched control subjects using a customized DNA microarray with enhanced sensitivity and specificity. Subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding (1) presynaptic regulators of GABA neurotransmission (67 kDa isoform of glutamic acid decarboxylase (GAD(67)) and GABA transporter 1), (2) neuropeptides (somatostatin (SST), neuropeptide Y (NPY) and cholecystokinin (CCK)) and (3) GABA(A) receptor subunits (alpha1, alpha4, beta3, gamma2 and delta). Real-time qPCR and/or in situ hybridization confirmed the deficits for six representative transcripts tested in the same pairs and in an extended cohort, respectively. In contrast, GAD(67), SST and alpha1 subunit mRNA levels, as assessed by in situ hybridization, were not altered in the DLPFC of monkeys chronically exposed to antipsychotic medications. These findings suggest that schizophrenia is associated with alterations in inhibitory inputs from SST/NPY-containing and CCK-containing subpopulations of GABA neurons and in the signaling via certain GABA(A) receptors that mediate synaptic (phasic) or extrasynaptic (tonic) inhibition. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia is mediated by altered GABA neurotransmission in certain DLPFC microcircuits.

Dataset Information

SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia.

Publications

SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets