MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects

• Published in: PloS one Vol. 7; no. 3; p. e33201
• Main Authors: Smalheiser, Neil R., Lugli, Giovanni, Rizavi, Hooriyah S., Torvik, Vetle I., Turecki, Gustavo, Dwivedi, Yogesh
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2012; Public Library of Science (PLoS)
• Subjects: Adenoviruses; Adult; Antidepressants; Biology; Biosynthesis; Blotting, Western; Brain; Brodmann's area; Cardiac arrest; Case-Control Studies; DEAD-box RNA Helicases - metabolism; Depression (Mood disorder); Depression - genetics; Depression - metabolism; DNA binding proteins; DNA Primers - genetics; Epigenetics; Female; Fibroblasts; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Genes; Genetic research; Genomes; Humans; Library and information science; Male; Medical research; Medicine; Mental depression; Mental disorders; MicroRNA; MicroRNAs; MicroRNAs - metabolism; Middle Aged; miRNA; Multiplex Polymerase Chain Reaction; Multiplexing; Neural plasticity; Neuroplasticity; Pathogenesis; Physics; Polymerase chain reaction; Prefrontal cortex; Prefrontal Cortex - metabolism; Proteins; Proteins - metabolism; Psychiatry; Quebec; Regulators; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease III - metabolism; Ribonucleic acid; RNA; RNA-Binding Proteins; Schizophrenia; Seeds; Statistical analysis; Statistics, Nonparametric; Studies; Suicidal behavior; Suicide; Transcription factors; Vascular endothelial growth factor; Quebec; United States > US; Illinois; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033201

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. 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. 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).