title: Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder.
abstract: Major depressive disorder (MDD) is predicted to be the second leading cause of global disease burden by 2030. A large number of MDD patients do not respond to the currently available medication because of its poorly understood etiology. Recently, studies of microRNAs (miRNAs), which act as a molecular switch of gene expression, have shown promise in identifying a molecular network that could provide significant clues to various psychiatric illnesses. Using an in vitro system, a rodent depression model, and a human postmortem brain, we investigated the role of a brain-enriched, neuron-specific miRNA, miR-124-3p, whose expression is highly dysregulated in stressed rodents, and identified a set of target genes involved in stress response and neural plasticity. We also found that miR-124-3p is epigenetically regulated and its interaction with the RNA-induced silencing complex (RISC) is compromised in MDD. Using blood serum, we found similar dysregulation of miR-124-3p in antidepressant-free MDD subjects. Altogether, our study demonstrates potential contribution of miR-124-3p in the pathophysiology of MDD and suggests that this miRNA may serve as a novel target for drug development and a biomarker for MDD pathogenesis.
authors: Translational Research, UAB Mood Disorder Program, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Bhaskar
authors: B
authors: Roy
authors: Translational Research, UAB Mood Disorder Program, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Michael
authors: M
authors: Dunbar
authors: Translational Research, UAB Mood Disorder Program, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Richard C
authors: RC
authors: Shelton
authors: Translational Research, UAB Mood Disorder Program, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Yogesh
authors: Y
authors: Dwivedi
mesh_terms: D000328:Adult; D000818:Animals; D003865:Major Depressive Disorder / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
chemical_list: C509207:MIRN124 microRNA, human; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs