{"id":18754,"date":"2016-09-13T22:46:53","date_gmt":"2016-09-14T02:46:53","guid":{"rendered":"http:\/\/therapytoronto.ca\/news\/?p=18754"},"modified":"2016-09-13T22:46:53","modified_gmt":"2016-09-14T02:46:53","slug":"a-microrna-plays-role-in-major-depression","status":"publish","type":"post","link":"https:\/\/therapytoronto.ca\/news\/2016\/09\/a-microrna-plays-role-in-major-depression\/","title":{"rendered":"A microRNA plays role in major depression"},"content":{"rendered":"<p>From the University of Alabama at Birmingham\u00a0media release:<\/p>\n<blockquote>\n<p id=\"first\" class=\"lead\"><strong><img loading=\"lazy\" class=\"alignright size-full wp-image-16264\" src=\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2014\/01\/DepressedSenior.jpg\" alt=\"Depressed senior\" width=\"300\" height=\"200\" \/>A tiny RNA appears to play a role in producing major depression<\/strong>, the mental disorder that affects as many as 250 million people a year worldwide.<\/p>\n<div id=\"text\">\n<p>Major depression, formally known as major depressive disorder, or MDD, brings increased risk of suicide and is reported to cause the second-most years of disability after low-back pain.<\/p>\n<p>University of Alabama at Birmingham researchers have found that <strong>amounts of this microRNA are significantly elevated in the brains of experimental rats with induced depression from corticosterone treatment<\/strong>, in the post-death brains of humans diagnosed with MDD and in peripheral blood serum from living patients with MDD, according to a study by led by Yogesh Dwivedi, Ph.D., the Elesabeth Ridgely Shook Endowed Professor and director of Translational Research, UAB Mood Disorders Program, Department of Psychiatry.<\/p>\n<p><strong>This microRNA &#8212; miR-124-3p &#8212; is thus a potential therapeutic target<\/strong> for novel drug development, and it can serve as a putative biomarker for MDD pathogenesis.<\/p>\n<p>Micro RNAs, or miRNAs, interact with messenger RNA after the miRNA is exported from the cell nucleus and processed by a team of enzymes. MiRNAs are robust players of gene regulation in cells, and there are more than 1,300 different miRNAs at work in the brain.<\/p>\n<p>In previous work, Dwivedi and colleagues had seen that a set of miRNAs were coordinately regulated in the prefrontal cortex of the brains of MDD subjects. <strong>The prefrontal cortex, known for controlling the executive function of the brain, is critically involved in the response to stress, by regulating the endocrine glands known as the hypothalamic-pituitary-adrenal axis<\/strong>. The adrenal gland produces the stress hormone cortisol in humans and corticosterone in rodents.<\/p>\n<p>To see if stress plays a role in the coordinated regulation of prefrontal cortex miRNAs, the UAB researchers then turned to a rat depression model. They found that rats treated with corticosterone to induce depression-like behavior showed coordinated dysregulation of miRNAs in the prefrontal cortex, and the most significantly affected miRNA was miR-124-3p.<\/p>\n<p>Their current paper, previewed in the journal <em>Neuropsychopharmacology<\/em>, examined the relevance of miR-124-3p in MDD pathogenesis.<\/p>\n<h3><strong>Using computer analysis of genome sequences, the researchers:<\/strong><\/h3>\n<ul>\n<li>Identified eight highly potential target genes for binding by miR-124-3p, genes whose function is also reported to be critical in brain physiology during stress and MDD pathogenesis. Four of these potential target genes were significantly down-regulated in the prefrontal cortex of corticosterone-treated rats, and this down-regulation inversely correlated with miR-124-3p levels.<\/li>\n<li>Showed that the four genes that were significantly down-regulated have evolutionarily conserved miR-124-3p binding sites across a wide range of higher vertebrate species.<\/li>\n<\/ul>\n<h3><strong>In neuroblastoma cells grown in culture:<\/strong><\/h3>\n<ul>\n<li>Overexpression of miR-124-3p caused significant down-regulation for two of the potential target genes.In prefrontal cortex neurons from depression-model rats treated with corticosterone:<\/li>\n<li>Significant binding by miR-124-3p to two of the potential target genes was seen, as measured from immunoprecipitated RNA-induced silencing complexes.<\/li>\n<li>The locus-specific origin of for mature miR-124-3p was identified at a site on chromosome 3, out of three possible chromosomal sites, and two CpG &#8220;islands&#8221; that can act as sites from epigenetic modification by DNA methylation were identified near the miR-124 gene promoter on chromosome 3.<\/li>\n<li>This miR-124-3 promoter was found to be hypo-methylated in the corticosterone-treated rats, and the gene expression of one DNA methyltransferase &#8212; Dnmt3a &#8212; was significantly repressed.<\/li>\n<\/ul>\n<h3><strong>For humans:<\/strong><\/h3>\n<ul>\n<li>In post-mortem brains of 15 controls and 15 MDD subjects, the MDD group showed significant increase in the expression of miR-124-3p, and expression of three of the potential target genes was significantly lower.<\/li>\n<li>The level of miR-124-3p was significantly higher in the serum of 18 antidepressant-free MDD patients, as compared with 17 healthy controls.<\/li>\n<\/ul>\n<p>&#8220;Altogether,&#8221; the UAB researchers conclude, &#8220;this is the first comprehensive and mechanistic study at in-vitro and in-vivo levels which demonstrates that, <strong>not only are there consistent depression-associated changes in the expression of miR-124-3p across different species, but also the genes that are targets of this miRNA are highly dysregulated, showing altered response at functional level<\/strong>.&#8221;<\/p>\n<\/div>\n<\/blockquote>\n<!-- AddThis Advanced Settings generic via filter on the_content --><!-- AddThis Share Buttons generic via filter on the_content -->","protected":false},"excerpt":{"rendered":"<p>From the University of Alabama at Birmingham\u00a0media release: A tiny RNA appears to play a role in producing major depression, the mental disorder that affects as many as 250 million&#8230; <a class=\"read-more-link\" href=\"https:\/\/therapytoronto.ca\/news\/2016\/09\/a-microrna-plays-role-in-major-depression\/\">Read more &raquo;<\/a><!-- AddThis Advanced Settings generic via filter on get_the_excerpt --><!-- AddThis Share Buttons generic via filter on get_the_excerpt --><\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[345],"tags":[42,14,234,49],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18754"}],"collection":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=18754"}],"version-history":[{"count":1,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18754\/revisions"}],"predecessor-version":[{"id":19191,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/18754\/revisions\/19191"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=18754"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=18754"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=18754"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}