MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects

Neil R. Smalheiser, Giovanni Lugli, Hooriyah S. Rizavi, Vetle I. Torvik, Gustavo Turecki, Yogesh Dwivedi

Research output: Contribution to journalArticle

Abstract

Background: Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases. Methodology/Principal Findings: The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5′-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group. Conclusions/Significance: The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).

Original languageEnglish (US)
Article numbere33201
JournalPloS one
Volume7
Issue number3
DOIs
StatePublished - Mar 9 2012

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suicide
Prefrontal Cortex
MicroRNAs
microRNA
Suicide
Depression
pathogenesis
prefrontal cortex
Gene Expression
gene expression
Messenger RNA
antidepressants
Neuronal Plasticity
Multiplex Polymerase Chain Reaction
Regulator Genes
regulator genes
human diseases
Gene expression
Antidepressive Agents
Plasticity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. / Smalheiser, Neil R.; Lugli, Giovanni; Rizavi, Hooriyah S.; Torvik, Vetle I.; Turecki, Gustavo; Dwivedi, Yogesh.

In: PloS one, Vol. 7, No. 3, e33201, 09.03.2012.

Research output: Contribution to journalArticle

Smalheiser, Neil R. ; Lugli, Giovanni ; Rizavi, Hooriyah S. ; Torvik, Vetle I. ; Turecki, Gustavo ; Dwivedi, Yogesh. / MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. In: PloS one. 2012 ; Vol. 7, No. 3.
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