Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects

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...

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Main Authors:	Smalheiser, Neil R., Lugli, Giovanni, Zhang, Hui, Rizavi, Hooriyah, Cook, Edwin H., Dwivedi, Yogesh
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903529/

id	pubmed-3903529
recordtype	oai_dc
spelling	pubmed-39035292014-01-28 Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects Smalheiser, Neil R. Lugli, Giovanni Zhang, Hui Rizavi, Hooriyah Cook, Edwin H. Dwivedi, Yogesh Research Article 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. Public Library of Science 2014-01-27 /pmc/articles/PMC3903529/ /pubmed/24475125 http://dx.doi.org/10.1371/journal.pone.0086469 Text en © 2014 Smalheiser et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Smalheiser, Neil R. Lugli, Giovanni Zhang, Hui Rizavi, Hooriyah Cook, Edwin H. Dwivedi, Yogesh
spellingShingle	Smalheiser, Neil R. Lugli, Giovanni Zhang, Hui Rizavi, Hooriyah Cook, Edwin H. Dwivedi, Yogesh Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
author_facet	Smalheiser, Neil R. Lugli, Giovanni Zhang, Hui Rizavi, Hooriyah Cook, Edwin H. Dwivedi, Yogesh
author_sort	Smalheiser, Neil R.
title	Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
title_short	Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
title_full	Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
title_fullStr	Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
title_full_unstemmed	Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects
title_sort	expression of micrornas and other small rnas in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects
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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903529/
_version_	1612051717045616640

Expression of microRNAs and Other Small RNAs in Prefrontal Cortex in Schizophrenia, Bipolar Disorder and Depressed Subjects

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